Category Archives: medicine

Lifesaving moths and nanomagnets

Rice University bioengineers use a magnetic field to activate nanoparticle-attached baculoviruses in a tissue. The viruses, which normally infect alfalfa looper moths, are modified to deliver gene-editing DNA code only to cells that are targeted with magnetic field-induced local transduction. Courtesy of the Laboratory of Biomolecular Engineering and Nanomedicine

Kudos to whomever put that diagram together! That’s a lot of well conveyed information.

Now for the details about how this technology might save lives. From a November 13, 2018 news item on Nanowerk,

A new technology that relies on a moth-infecting virus and nanomagnets could be used to edit defective genes that give rise to diseases like sickle cell, muscular dystrophy and cystic fibrosis.

Rice University bioengineer Gang Bao has combined magnetic nanoparticles with a viral container drawn from a particular species of moth to deliver CRISPR/Cas9 payloads that modify genes in a specific tissue or organ with spatial control.

A November 12, 2018 Rice University news release (also on EurekAlert published on November 13, 2018), which originated the news item, provides detail,

Because magnetic fields are simple to manipulate and, unlike light, pass easily through tissue, Bao and his colleagues want to use them to control the expression of viral payloads in target tissues by activating the virus that is otherwise inactivated in blood.

The research appears in Nature Biomedical Engineering. In nature, CRISPR/Cas9 bolsters microbes’ immune systems by recording the DNA of invaders. That gives microbes the ability to recognize and attack returning invaders, but scientists have been racing to adapt CRISPR/Cas9 to repair mutations that cause genetic diseases and to manipulate DNA in laboratory experiments.

CRISPR/Cas9 has the potential to halt hereditary disease – if scientists can get the genome-editing machinery to the right cells inside the body. But roadblocks remain, especially in delivering the gene-editing payloads with high efficiency.

Bao said it will be necessary to edit cells in the body to treat many diseases. “But efficiently delivering genome-editing machinery into target tissue in the body with spatial control remains a major challenge,” Bao said. “Even if you inject the viral vector locally, it can leak to other tissues and organs, and that could be dangerous.”

The delivery vehicle developed by Bao’s group is based on a virus that infects Autographa californica, aka the alfalfa looper, a moth native to North America. The cylindrical baculovirus vector (BV), the payload-carrying part of the virus, is considered large at up to 60 nanometers in diameter and 200-300 nanometers in length. That’s big enough to transport more than 38,000 base pairs of DNA, which is enough to supply multiple gene-editing units to a target cell, Bao said.

He said the inspiration to combine BV and magnetic nanoparticles came from discussions with Rice postdoctoral researcher and co-lead author Haibao Zhu, who learned about the virus during a postdoctoral stint in Singapore but knew nothing about magnetic nanoparticles until he joined the Bao lab. The Rice team had previous experience using iron oxide nanoparticles and an applied magnetic field to open blood vessel walls just enough to let large-molecule drugs pass through.

“We really didn’t know if this would work for gene editing or not, but we thought, ‘worth a shot,'” Bao said.

The researchers use the magnetic nanoparticles to activate BV and deliver gene-editing payloads only where they’re needed. To do this, they take advantage of an immune-system protein called C3 that normally inactivates baculoviruses.

“If we combine BV with magnetic nanoparticles, we can overcome this deactivation by applying the magnetic field,” Bao said. “The beauty is that when we deliver it, gene editing occurs only at the tissue, or the part of the tissue, where we apply the magnetic field.”

Application of the magnetic field allows BV transduction, the payload-delivery process that introduces gene-editing cargo into the target cell. The payload is also DNA, which encodes both a reporter gene and the CRISPR/Cas9 system.

In tests, the BV was loaded with green fluorescent proteins or firefly luciferase. Cells with the protein glowed brightly under a microscope, and experiments showed the magnets were highly effective at targeted delivery of BV cargoes in both cell cultures and lab animals.

Bao noted his and other labs are working on the delivery of CRISPR/Cas9 with adeno-associated viruses (AAV), but he said BV’s capacity for therapeutic cargo is roughly eight times larger. “However, it is necessary to make BV transduction into target cells more efficient,” he said.

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

Spatial control of in vivo CRISPR–Cas9 genome editing via nanomagnets by Haibao Zhu, Linlin Zhang, Sheng Tong, Ciaran M. Lee, Harshavardhan Deshmukh, & Gang Bao. Nature Biomedical Engineering (2018) DOI: https://doi.org/10.1038/s41551-018-0318-7 Published: 12 November 2018

This paper is behind a paywall.

Wearable electronic textiles from the UK, India, and Canada: two different carbon materials

It seems wearable electronic textiles may be getting nearer to the marketplace. I have three research items (two teams working with graphene and one working with carbon nanotubes) that appeared on my various feeds within two days of each other.

UK/China

This research study is the result of a collaboration between UK and Chinese scientists. From a May 15, 2019 news item on phys.org (Note: Links have been removed),


Wearable electronic components incorporated directly into fabrics have been developed by researchers at the University of Cambridge. The devices could be used for flexible circuits, healthcare monitoring, energy conversion, and other applications.

The Cambridge researchers, working in collaboration with colleagues at Jiangnan University in China, have shown how graphene – a two-dimensional form of carbon – and other related materials can be directly incorporated into fabrics to produce charge storage elements such as capacitors, paving the way to textile-based power supplies which are washable, flexible and comfortable to wear.

The research, published in the journal Nanoscale, demonstrates that graphene inks can be used in textiles able to store electrical charge and release it when required. The new textile electronic devices are based on low-cost, sustainable and scalable dyeing of polyester fabric. The inks are produced by standard solution processing techniques.

Building on previous work by the same team, the researchers designed inks which can be directly coated onto a polyester fabric in a simple dyeing process. The versatility of the process allows various types of electronic components to be incorporated into the fabric.

Schematic of the textile-based capacitor integrating GNP/polyesters as electrodes and h-BN/polyesters as dielectrics. Credit: Felice Torrisi

A May 16, 2019 University of Cambridge press release, which originated the news item, probes further,

Most other wearable electronics rely on rigid electronic components mounted on plastic or textiles. These offer limited compatibility with the skin in many circumstances, are damaged when washed and are uncomfortable to wear because they are not breathable.

“Other techniques to incorporate electronic components directly into textiles are expensive to produce and usually require toxic solvents, which makes them unsuitable to be worn,” said Dr Felice Torrisi from the Cambridge Graphene Centre, and the paper’s corresponding author. “Our inks are cheap, safe and environmentally-friendly, and can be combined to create electronic circuits by simply overlaying different fabrics made of two-dimensional materials on the fabric.”

The researchers suspended individual graphene sheets in a low boiling point solvent, which is easily removed after deposition on the fabric, resulting in a thin and uniform conducting network made up of multiple graphene sheets. The subsequent overlay of several graphene and hexagonal boron nitride (h-BN) fabrics creates an active region, which enables charge storage. This sort of ‘battery’ on fabric is bendable and can withstand washing cycles in a normal washing machine.

“Textile dyeing has been around for centuries using simple pigments, but our result demonstrates for the first time that inks based on graphene and related materials can be used to produce textiles that could store and release energy,” said co-author Professor Chaoxia Wang from Jiangnan University in China. “Our process is scalable and there are no fundamental obstacles to the technological development of wearable electronic devices both in terms of their complexity and performance.”

The work done by the Cambridge researchers opens a number of commercial opportunities for ink based on two-dimensional materials, ranging from personal health and well-being technology, to wearable energy and data storage, military garments, wearable computing and fashion.

“Turning textiles into functional energy storage elements can open up an entirely new set of applications, from body-energy harvesting and storage to the Internet of Things,” said Torrisi “In the future our clothes could incorporate these textile-based charge storage elements and power wearable textile devices.”

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

Wearable solid-state capacitors based on two-dimensional material all-textile heterostructures by Siyu Qiang, Tian Carey, Adrees Arbab, Weihua Song, Chaoxia Wang and Felice Torris. Nanoscale, 2019, Advance Article DOI: 10.1039/C9NR00463G First published on 18 Apr 2019

This paper is behind a paywall.

India

Prior to graphene’s reign as the ‘it’ carbon material, carbon nanotubes (CNTs) ruled. It’s been quieter on the CNT front since graphene took over but a May 15, 2019 Nanowerk Spotlight article by Michael Berger highlights some of the latest CNT research coming out of India,


The most important technical challenge is to blend the chemical nature of raw materials with fabrication techniques and processability, all of which are diametrically conflicting for textiles and conventional energy storage devices. A team from Indian Institute of Technology Bombay has come out with a comprehensive approach involving simple and facile steps to fabricate a wearable energy storage device. Several scientific and technological challenges were overcome during this process.

First, to achieve user-comfort and computability with clothing, the scaffold employed was the the same as what a regular fabric is made up of – cellulose fibers. However, cotton yarns are electrical insulators and therefore practically useless for any electronics. Therefore, the yarns are coated with single-wall carbon nanotubes (SWNTs).

SWNTs are hollow, cylindrical allotropes of carbon and combine excellent mechanical strength with electrical conductivity and surface area. Such a coating converts the electrical insulating cotton yarn to a metallic conductor with high specific surface area. At the same time, using carbon-based materials ensures that the final material remains light-weight and does not cause user discomfort that can arise from metallic wires such as copper and gold. This CNT-coated cotton yarn (CNT-wires) forms the electrode for the energy storage device.

Next, the electrolyte is composed of solid-state electrolyte sheets since no liquid-state electrolytes can be used for this purpose. However, solid state electrolytes suffer from poor ionic conductivity – a major disadvantage for energy storage applications. Therefore, a steam-based infiltration approach that enhances the ionic conductivity of the electrolyte is adopted. Such enhancement of humidity significantly increases the energy storage capacity of the device.


The integration of the CNT-wire electrode with the electrolyte sheet was carried out by a simple and elegant approach of interweaving the CNT-wire through the electrolyte (see Figure 1). This resulted in cross-intersections which are actually junctions where the electrical energy can be stored. Each such junction is now an energy storage unit, referred to as sewcap.

The advantage of this process is that several 100s and 1000s of sewcaps can be made in a small area and integrated to increase the total amount of energy stored in the system. This scalability is unique and critical aspect of this work and stems from the approach of interweaving.

Further, this process is completely adaptable with current processes used in textile industries. Hence, a proportionately large energy-storage is achieved by creating sewcap-junctions in various combinations.

All components of the final sewcap device are flexible. However, they need to be protected from environmental effects such as temperature, humidity and sweat while retaining the mechanical flexibility. This is achieved by laminating the entire device between polymer sheets. The process is exactly similar to the one used for protecting documents and ID cards.

The laminated sewcap can be integrated easily on clothing and fabrics while retaining the flexibility and sturdiness. This is demonstrated by the unchanged performance of the device during extreme and harsh mechanical testing such as striking repeatedly with a hammer, complete flexing, bending and rolling and washing in a laundry machine.

In fact, this is the first device that has been proven to be stable under rigorous washing conditions in the presence of hot water, detergents and high torque (spinning action of washing machine). This provides the device with comprehensive mechanical stability.


CNTs have high surface area and electrical conductivity. The CNT-wire combines these properties of CNTs with stability and porosity of cellulose yarns. The junction created by interweaving is essentially comprised of two such CNT-wires that are sandwiching an electrolyte. Application of potential difference leads to polarization of the electrolyte thus enabling energy storage similar to the way in which a conventional capacitor acts.

“We use the advantage of the interweaving process and create several such junctions. So, with each junction being able to store a certain amount of electrical energy, all the junctions synchronized are able to store a large amount of energy. This provides high energy density to the device,” Prof. C. Subramaniam, Department of Chemistry, IIT Bombay and corresponding author of the paper points out.

The device has also been employed for lighting up an LED [light-emitting diode]. This can be potentially scaled to provide electrical energy demanded by the application.

This image accompanies the paper written by Prof. C. Subramaniam and his team,

Courtesy: IACS Applied Materials Interfaces

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

Interwoven Carbon Nanotube Wires for High-Performing, Mechanically Robust, Washable, and Wearable Supercapacitors by Mihir Kumar Jha, Kenji Hata, and Chandramouli Subramaniam. ACS Appl. Mater. Interfaces, Article ASAP DOI: 10.1021/acsami.8b22233 Publication Date (Web): April 29, 2019 Copyright © 2019 American Chemical Society

This paper is behind a paywall.

Canada

A research team from the University of British Columbia (UBC at the Okanagan Campus) joined the pack with a May 16, 2019 news item on ScienceDaily,

Forget the smart watch. Bring on the smart shirt.

Researchers at UBC Okanagan’s School of Engineering have developed a low-cost sensor that can be interlaced into textiles and composite materials. While the research is still new, the sensor may pave the way for smart clothing that can monitor human movement.

A May 16, 2019 UBC news release (also on EurekAlert), which originated the news item, describes the work in more detail,


“Microscopic sensors are changing the way we monitor machines and humans,” says Hoorfar, lead researcher at the Advanced Thermo-Fluidic Lab at UBC’s Okanagan campus. “Combining the shrinking of technology along with improved accuracy, the future is very bright in this area.”

This ‘shrinking technology’ uses a phenomenon called piezo-resistivity—an electromechanical response of a material when it is under strain. These tiny sensors have shown a great promise in detecting human movements and can be used for heart rate monitoring or temperature control, explains Hoorfar.

Her research, conducted in partnership with UBC Okanagan’s Materials and Manufacturing Research Institute, shows the potential of a low-cost, sensitive and stretchable yarn sensor. The sensor can be woven into spandex material and then wrapped into a stretchable silicone sheath. This sheath protects the conductive layer against harsh conditions and allows for the creation of washable wearable sensors.

While the idea of smart clothing—fabrics that can tell the user when to hydrate, or when to rest—may change the athletics industry, UBC Professor Abbas Milani says the sensor has other uses. It can monitor deformations in fibre-reinforced composite fabrics currently used in advanced industries such as automotive, aerospace and marine manufacturing.

The low-cost stretchable composite sensor has also shown a high sensitivity and can detect small deformations such as yarn stretching as well as out-of-plane deformations at inaccessible places within composite laminates, says Milani, director of the UBC Materials and Manufacturing Research Institute.

The testing indicates that further improvements in its accuracy could be achieved by fine-tuning the sensor’s material blend and improving its electrical conductivity and sensitivity This can eventually make it able to capture major flaws like “fibre wrinkling” during the manufacturing of advanced composite structures such as those currently used in airplanes or car bodies.

“Advanced textile composite materials make the most of combining the strengths of different reinforcement materials and patterns with different resin options,” he says. “Integrating sensor technologies like piezo-resistive sensors made of flexible materials compatible with the host textile reinforcement is becoming a real game-changer in the emerging era of smart manufacturing and current automated industry trends.”

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

Graphene‐Coated Spandex Sensors Embedded into Silicone Sheath for Composites Health Monitoring and Wearable Applications by Hossein Montazerian, Armin Rashidi, Arash Dalili, Homayoun Najjaran, Abbas S. Milani, Mina Hoorfar. Small Volume15, Issue17 April 26, 2019 1804991 DOI: https://doi.org/10.1002/smll.201804991 First published: 28 March 2019

This paper is behind a paywall.

Will there be one winner or will they find CNTs better for one type of wearable tech textile while graphene excels for another type of wearable tech textile?

Snakebite? Roll out the nanoparticles

An October 4, 2018 news item on Nanowerk highlights some recent research into treating snakebites (Note: A link has been removed),

Venomous snakebites affect 2.5 million people, and annually cause more than 100,000 deaths and leave 400,000 individuals with permanent physical and psychological trauma each year.

Researchers reporting in PLOS Neglected Tropical Diseases (“Engineered nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis”) have now described a new approach to treating snake bites [sic], using nanoparticles to bind to venom toxins and prevent the spread of venom through the body.

Caption: “Synthetic polymer nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis.” Credit: Shea, et al. CC BY 4.0: Redistribution allowed with credit

An October 4, 2018 PLOS news release on EurekAlert, which originated the news item, expands on the theme,

The standard treatment for snakebites is the intravenous administration of IgG immune molecules that recognize venoms. However, such antivenom therapies must be administered quickly–and by trained healthcare workers– to be effective and are highly specific to particular venoms. There is an ongoing need for a snakebite treatment which can be used in a rural setting and works against the bites of diverse venomous snakes.

In the new work, Kenneth Shea, of the University of California, Irvine, and colleagues engineered nanoparticles that bind to and sequester an array of phospholipases A2 (PLA2) and three-finger toxin (3FTX) molecules found in Elapidae snake venoms. The Elapidae family is a large family of venomous snakes that includes cobras, kraits, tiger snakes, sea snakes, coral snakes and mambas, among other species. The researchers tested the ability of the nanoparticles to block Naja nigricollis (black-necked spitting cobra) venom in mice that received varying doses of the nanoparticles, injected into the skin. Envenomings by this snake in sub-Saharan Africa inflict serious cutaneous necrosis that may leave permanent tissue damage in the victims.

In experiments on isolated cells, the nanoparticles were found to sequester a wide range of Elapidae PLA and 3FTX venoms. Moreover, with collaborator José María Gutiérrez from the Instituto Clodomiro Picado (Universidad de Costa Rica), experiments with mice demonstrated that injections of the nanoparticles at the site of venom injection significantly mitigated the typical necrotic effects–including blistering and ulcers– of the spitting cobra venom. The nanoparticles administered to mice that had not received venom did not have an effect on skin and did not induce systemic toxicity.

“The stable, low-cost nanoparticles have the potential to be administered subcutaneously immediately after the bite at the site of envenoming by this spitting cobra to halt or reduce the extent of local damage and mitigate the systemic distribution of toxins post-envenoming,” the researchers say.

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

Engineered nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis by Jeffrey O’Brien, Shih-Hui Lee, José María Gutiérrez, Kenneth J. Shea. PLOS Neglected Tropical Diseases 12(10): e0006736 DOI: https://doi.org/10.1371/journal.pntd.0006736 Published: October 4, 2018

This paper is open access. By the way, PLOS stands for Public Library of Science.

Gene editing and personalized medicine: Canada

Back in the fall of 2018 I came across one of those overexcited pieces about personalized medicine and gene editing tha are out there. This one came from an unexpected source, an author who is a “PhD Scientist in Medical Science (Blood and Vasculature” (from Rick Gierczak’s LinkedIn profile).

It starts our promisingly enough although I’m beginning to dread the use of the word ‘precise’  where medicine is concerned, (from a September 17, 2018 posting on the Science Borealis blog by Rick Gierczak (Note: Links have been removed),

CRISPR-Cas9 technology was accidentally discovered in the 1980s when scientists were researching how bacteria defend themselves against viral infection. While studying bacterial DNA called clustered regularly interspaced short palindromic repeats (CRISPR), they identified additional CRISPR-associated (Cas) protein molecules. Together, CRISPR and one of those protein molecules, termed Cas9, can locate and cut precise regions of bacterial DNA. By 2012, researchers understood that the technology could be modified and used more generally to edit the DNA of any plant or animal. In 2015, the American Association for the Advancement of Science chose CRISPR-Cas9 as science’s “Breakthrough of the Year”.

Today, CRISPR-Cas9 is a powerful and precise gene-editing tool [emphasis mine] made of two molecules: a protein that cuts DNA (Cas9) and a custom-made length of RNA that works like a GPS for locating the exact spot that needs to be edited (CRISPR). Once inside the target cell nucleus, these two molecules begin editing the DNA. After the desired changes are made, they use a repair mechanism to stitch the new DNA into place. Cas9 never changes, but the CRISPR molecule must be tailored for each new target — a relatively easy process in the lab. However, it’s not perfect, and occasionally the wrong DNA is altered [emphasis mine].

Note that Gierczak makes a point of mentioning that CRISPR/Cas9 is “not perfect.” And then, he gets excited (Note: Links have been removed),

CRISPR-Cas9 has the potential to treat serious human diseases, many of which are caused by a single “letter” mutation in the genetic code (A, C, T, or G) that could be corrected by precise editing. [emphasis mine] Some companies are taking notice of the technology. A case in point is CRISPR Therapeutics, which recently developed a treatment for sickle cell disease, a blood disorder that causes a decrease in oxygen transport in the body. The therapy targets a special gene called fetal hemoglobin that’s switched off a few months after birth. Treatment involves removing stem cells from the patient’s bone marrow and editing the gene to turn it back on using CRISPR-Cas9. These new stem cells are returned to the patient ready to produce normal red blood cells. In this case, the risk of error is eliminated because the new cells are screened for the correct edit before use.

The breakthroughs shown by companies like CRISPR Therapeutics are evidence that personalized medicine has arrived. [emphasis mine] However, these discoveries will require government regulatory approval from the countries where the treatment is going to be used. In the US, the Food and Drug Administration (FDA) has developed new regulations allowing somatic (i.e., non-germ) cell editing and clinical trials to proceed. [emphasis mine]

The potential treatment for sickle cell disease is exciting but Gierczak offers no evidence that this treatment or any unnamed others constitute proof that “personalized medicine has arrived.” In fact, Goldman Sachs, a US-based investment bank, makes the case that it never will .

Cost/benefit analysis

Edward Abrahams, president of the Personalized Medicine Coalition (US-based), advocates for personalized medicine while noting in passing, market forces as represented by Goldman Sachs in his May 23, 2018 piece for statnews.com (Note: A link has been removed),

One of every four new drugs approved by the Food and Drug Administration over the last four years was designed to become a personalized (or “targeted”) therapy that zeros in on the subset of patients likely to respond positively to it. That’s a sea change from the way drugs were developed and marketed 10 years ago.

Some of these new treatments have extraordinarily high list prices. But focusing solely on the cost of these therapies rather than on the value they provide threatens the future of personalized medicine.

… most policymakers are not asking the right questions about the benefits of these treatments for patients and society. Influenced by cost concerns, they assume that prices for personalized tests and treatments cannot be justified even if they make the health system more efficient and effective by delivering superior, longer-lasting clinical outcomes and increasing the percentage of patients who benefit from prescribed treatments.

Goldman Sachs, for example, issued a report titled “The Genome Revolution.” It argues that while “genome medicine” offers “tremendous value for patients and society,” curing patients may not be “a sustainable business model.” [emphasis mine] The analysis underlines that the health system is not set up to reap the benefits of new scientific discoveries and technologies. Just as we are on the precipice of an era in which gene therapies, gene-editing, and immunotherapies promise to address the root causes of disease, Goldman Sachs says that these therapies have a “very different outlook with regard to recurring revenue versus chronic therapies.”

Let’s just chew on this one (contemplate)  for a minute”curing patients may not be ‘sustainable business model’!”

Coming down to earth: policy

While I find Gierczak to be over-enthused, he, like Abrahams, emphasizes the importance of new policy, in his case, the focus is Canadian policy. From Gierczak’s September 17, 2018 posting (Note: Links have been removed),

In Canada, companies need approval from Health Canada. But a 2004 law called the Assisted Human Reproduction Act (AHR Act) states that it’s a criminal offence “to alter the genome of a human cell, or in vitroembryo, that is capable of being transmitted to descendants”. The Actis so broadly written that Canadian scientists are prohibited from using the CRISPR-Cas9 technology on even somatic cells. Today, Canada is one of the few countries in the world where treating a disease with CRISPR-Cas9 is a crime.

On the other hand, some countries provide little regulatory oversight for editing either germ or somatic cells. In China, a company often only needs to satisfy the requirements of the local hospital where the treatment is being performed. And, if germ-cell editing goes wrong, there is little recourse for the future generations affected.

The AHR Act was introduced to regulate the use of reproductive technologies like in vitrofertilization and research related to cloning human embryos during the 1980s and 1990s. Today, we live in a time when medical science, and its role in Canadian society, is rapidly changing. CRISPR-Cas9 is a powerful tool, and there are aspects of the technology that aren’t well understood and could potentially put patients at risk if we move ahead too quickly. But the potential benefits are significant. Updated legislation that acknowledges both the risks and current realities of genomic engineering [emphasis mine] would relieve the current obstacles and support a path toward the introduction of safe new therapies.

Criminal ban on human gene-editing of inheritable cells (in Canada)

I had no idea there was a criminal ban on the practice until reading this January 2017 editorial by Bartha Maria Knoppers, Rosario Isasi, Timothy Caulfield, Erika Kleiderman, Patrick Bedford, Judy Illes, Ubaka Ogbogu, Vardit Ravitsky, & Michael Rudnicki for (Nature) npj Regenerative Medicine (Note: Links have been removed),

Driven by the rapid evolution of gene editing technologies, international policy is examining which regulatory models can address the ensuing scientific, socio-ethical and legal challenges for regenerative and personalised medicine.1 Emerging gene editing technologies, including the CRISPR/Cas9 2015 scientific breakthrough,2 are powerful, relatively inexpensive, accurate, and broadly accessible research tools.3 Moreover, they are being utilised throughout the world in a wide range of research initiatives with a clear eye on potential clinical applications. Considering the implications of human gene editing for selection, modification and enhancement, it is time to re-examine policy in Canada relevant to these important advances in the history of medicine and science, and the legislative and regulatory frameworks that govern them. Given the potential human reproductive applications of these technologies, careful consideration of these possibilities, as well as ethical and regulatory scrutiny must be a priority.4

With the advent of human embryonic stem cell research in 1978, the birth of Dolly (the cloned sheep) in 1996 and the Raelian cloning hoax in 2003, the environment surrounding the enactment of Canada’s 2004 Assisted Human Reproduction Act (AHRA) was the result of a decade of polarised debate,5 fuelled by dystopian and utopian visions for future applications. Rightly or not, this led to the AHRA prohibition on a wide range of activities, including the creation of embryos (s. 5(1)(b)) or chimeras (s. 5(1)(i)) for research and in vitro and in vivo germ line alterations (s. 5(1)(f)). Sanctions range from a fine (up to $500,000) to imprisonment (up to 10 years) (s. 60 AHRA).

In Canada, the criminal ban on gene editing appears clear, the Act states that “No person shall knowingly […] alter the genome of a cell of a human being or in vitro embryo such that the alteration is capable of being transmitted to descendants;” [emphases mine] (s. 5(1)(f) AHRA). This approach is not shared worldwide as other countries such as the United Kingdom, take a more regulatory approach to gene editing research.1 Indeed, as noted by the Law Reform Commission of Canada in 1982, criminal law should be ‘an instrument of last resort’ used solely for “conduct which is culpable, seriously harmful, and generally conceived of as deserving of punishment”.6 A criminal ban is a suboptimal policy tool for science as it is inflexible, stifles public debate, and hinders responsiveness to the evolving nature of science and societal attitudes.7 In contrast, a moratorium such as the self-imposed research moratorium on human germ line editing called for by scientists in December 20158 can at least allow for a time limited pause. But like bans, they may offer the illusion of finality and safety while halting research required to move forward and validate innovation.

On October 1st, 2016, Health Canada issued a Notice of Intent to develop regulations under the AHRA but this effort is limited to safety and payment issues (i.e. gamete donation). Today, there is a need for Canada to revisit the laws and policies that address the ethical, legal and social implications of human gene editing. The goal of such a critical move in Canada’s scientific and legal history would be a discussion of the right of Canadians to benefit from the advancement of science and its applications as promulgated in article 27 of the Universal Declaration of Human Rights9 and article 15(b) of the International Covenant on Economic, Social and Cultural Rights,10 which Canada has signed and ratified. Such an approach would further ensure the freedom of scientific endeavour both as a principle of a liberal democracy and as a social good, while allowing Canada to be engaged with the international scientific community.

Even though it’s a bit old, I still recommend reading the open access editorial in full, if you have the time.

One last thing abut the paper, the acknowledgements,

Sponsored by Canada’s Stem Cell Network, the Centre of Genomics and Policy of McGill University convened a ‘think tank’ on the future of human gene editing in Canada with legal and ethics experts as well as representatives and observers from government in Ottawa (August 31, 2016). The experts were Patrick Bedford, Janetta Bijl, Timothy Caulfield, Judy Illes, Rosario Isasi, Jonathan Kimmelman, Erika Kleiderman, Bartha Maria Knoppers, Eric Meslin, Cate Murray, Ubaka Ogbogu, Vardit Ravitsky, Michael Rudnicki, Stephen Strauss, Philip Welford, and Susan Zimmerman. The observers were Geneviève Dubois-Flynn, Danika Goosney, Peter Monette, Kyle Norrie, and Anthony Ridgway.

Competing interests

The authors declare no competing interests.

Both McGill and the Stem Cell Network pop up again. A November 8, 2017 article about the need for new Canadian gene-editing policies by Tom Blackwell for the National Post features some familiar names (Did someone have a budget for public relations and promotion?),

It’s one of the most exciting, and controversial, areas of health science today: new technology that can alter the genetic content of cells, potentially preventing inherited disease — or creating genetically enhanced humans.

But Canada is among the few countries in the world where working with the CRISPR gene-editing system on cells whose DNA can be passed down to future generations is a criminal offence, with penalties of up to 10 years in jail.

This week, one major science group announced it wants that changed, calling on the federal government to lift the prohibition and allow researchers to alter the genome of inheritable “germ” cells and embryos.

The potential of the technology is huge and the theoretical risks like eugenics or cloning are overplayed, argued a panel of the Stem Cell Network.

The step would be a “game-changer,” said Bartha Knoppers, a health-policy expert at McGill University, in a presentation to the annual Till & McCulloch Meetings of stem-cell and regenerative-medicine researchers [These meetings were originally known as the Stem Cell Network’s Annual General Meeting {AGM}]. [emphases mine]

“I’m completely against any modification of the human genome,” said the unidentified meeting attendee. “If you open this door, you won’t ever be able to close it again.”

If the ban is kept in place, however, Canadian scientists will fall further behind colleagues in other countries, say the experts behind the statement say; they argue possible abuses can be prevented with good ethical oversight.

“It’s a human-reproduction law, it was never meant to ban and slow down and restrict research,” said Vardit Ravitsky, a University of Montreal bioethicist who was part of the panel. “It’s a sort of historical accident … and now our hands are tied.”

There are fears, as well, that CRISPR could be used to create improved humans who are genetically programmed to have certain facial or other features, or that the editing could have harmful side effects. Regardless, none of it is happening in Canada, good or bad.

In fact, the Stem Cell Network panel is arguably skirting around the most contentious applications of the technology. It says it is asking the government merely to legalize research for its own sake on embryos and germ cells — those in eggs and sperm — not genetic editing of embryos used to actually get women pregnant.

The highlighted portions in the last two paragraphs of the excerpt were written one year prior to the claims by a Chinese scientist that he had run a clinical trial resulting in gene-edited twins, Lulu and Nana. (See my my November 28, 2018 posting for a comprehensive overview of the original furor). I have yet to publish a followup posting featuring the news that the CRISPR twins may have been ‘improved’ more extensively than originally realized. The initial reports about the twins focused on an illness-related reason (making them HIV ‘immune’) but made no mention of enhanced cognitive skills a side effect of eliminating the gene that would make them HIV ‘immune’. To date, the researcher has not made the bulk of his data available for an in-depth analysis to support his claim that he successfully gene-edited the twins. As well, there were apparently seven other pregnancies coming to term as part of the researcher’s clinical trial and there has been no news about those births.

Risk analysis innovation

Before moving onto the innovation of risk analysis, I want to focus a little more on at least one of the risks that gene-editing might present. Gierczak noted that CRISPR/Cas9 is “not perfect,” which acknowledges the truth but doesn’t convey all that much information.

While the terms ‘precision’ and ‘scissors’ are used frequently when describing the CRISPR technique, scientists actually mean that the technique is significantly ‘more precise’ than other techniques but they are not referencing an engineering level of precision. As for the ‘scissors’, it’s an analogy scientists like to use but in fact CRISPR is not as efficient and precise as a pair of scissors.

Michael Le Page in a July 16, 2018 article for New Scientist lays out some of the issues (Note: A link has been removed),

A study of CRIPSR suggests we shouldn’t rush into trying out CRISPR genome editing inside people’s bodies just yet. The technique can cause big deletions or rearrangements of DNA [emphasis mine], says Allan Bradley of the Wellcome Sanger Institute in the UK, meaning some therapies based on CRISPR may not be quite as safe as we thought.

The CRISPR genome editing technique is revolutionising biology, enabling us to create new varieties of plants and animals and develop treatments for a wide range of diseases.

The CRISPR Cas9 protein works by cutting the DNA of a cell in a specific place. When the cell repairs the damage, a few DNA letters get changed at this spot – an effect that can be exploited to disable genes.

At least, that’s how it is supposed to work. But in studies of mice and human cells, Bradley’s team has found that in around a fifth of cells, CRISPR causes deletions or rearrangements more than 100 DNA letters long. These surprising changes are sometimes thousands of letters long.

“I do believe the findings are robust,” says Gaetan Burgio of the Australian National University, an expert on CRISPR who has debunked previous studies questioning the method’s safety. “This is a well-performed study and fairly significant.”

I covered the Bradley paper and the concerns in a July 17, 2018 posting ‘The CRISPR ((clustered regularly interspaced short palindromic repeats)-CAS9 gene-editing technique may cause new genetic damage kerfuffle‘. (The ‘kerfufle’ was in reference to a report that the CRISPR market was affected by the publication of Bradley’s paper.)

Despite Health Canada not moving swiftly enough for some researchers, they have nonetheless managed to release an ‘outcome’ report about a consultation/analysis started in October 2016. Before getting to the consultation’s outcome, it’s interesting to look at how the consultation’s call for response was described (from Health Canada’s Toward a strengthened Assisted Human Reproduction Act ; A Consultation with Canadians on Key Policy Proposals webpage),

In October 2016, recognizing the need to strengthen the regulatory framework governing assisted human reproduction in Canada, Health Canada announced its intention to bring into force the dormant sections of the Assisted Human Reproduction Act  and to develop the necessary supporting regulations.

This consultation document provides an overview of the key policy proposals that will help inform the development of regulations to support bringing into force Section 10, Section 12 and Sections 45-58 of the Act. Specifically, the policy proposals describe the Department’s position on the following:

Section 10: Safety of Donor Sperm and Ova

  • Scope and application
  • Regulated parties and their regulatory obligations
  • Processing requirements, including donor suitability assessment
  • Record-keeping and traceability

Section 12: Reimbursement

  • Expenditures that may be reimbursed
  • Process for reimbursement
  • Creation and maintenance of records

Sections 45-58: Administration and Enforcement

  • Scope of the administration and enforcement framework
  • Role of inspectors designated under the Act

The purpose of the document is to provide Canadians with an opportunity to review the policy proposals and to provide feedback [emphasis mine] prior to the Department finalizing policy decisions and developing the regulations. In addition to requesting stakeholders’ general feedback on the policy proposals, the Department is also seeking input on specific questions, which are included throughout the document.

It took me a while to find the relevant section (in particular, take note of ‘Federal Regulatory Oversight’),

3.2. AHR in Canada Today

Today, an increasing number of Canadians are turning to AHR technologies to grow or build their families. A 2012 Canadian studyFootnote 1 found that infertility is on the rise in Canada, with roughly 16% of heterosexual couples experiencing infertility. In addition to rising infertility, the trend of delaying marriage and parenthood, scientific advances in cryopreserving ova, and the increasing use of AHR by LGBTQ2 couples and single parents to build a family are all contributing to an increase in the use of AHR technologies.

The growing use of reproductive technologies by Canadians to help build their families underscores the need to strengthen the AHR Act. While the approach to regulating AHR varies from country to country, Health Canada has considered international best practices and the need for regulatory alignment when developing the proposed policies set out in this document. …

3.2.1 Federal Regulatory Oversight

Although the scope of the AHR Act was significantly reduced in 2012 and some of the remaining sections have not yet been brought into force, there are many important sections of the Act that are currently administered and enforced by Health Canada, as summarized generally below:

Section 5: Prohibited Scientific and Research Procedures
Section 5 prohibits certain types of scientific research and clinical procedures that are deemed unacceptable, including: human cloning, the creation of an embryo for non-reproductive purposes, maintaining an embryo outside the human body beyond the fourteenth day, sex selection for non-medical reasons, altering the genome in a way that could be transmitted to descendants, and creating a chimera or a hybrid. [emphasis mine]

….

It almost seems as if the they were hiding the section that broached the human gene-editing question. It doesn’t seem to have worked as it appears, there are some very motivated parties determined to reframe the discussion. Health Canada’s ‘outocme’ report, published March 2019, What we heard: A summary of scanning and consultations on what’s next for health product regulation reflects the success of those efforts,

1.0 Introduction and Context

Scientific and technological advances are accelerating the pace of innovation. These advances are increasingly leading to the development of health products that are better able to predict, define, treat, and even cure human diseases. Globally, many factors are driving regulators to think about how to enable health innovation. To this end, Health Canada has been expanding beyond existing partnerships and engaging both domestically and internationally. This expanding landscape of products and services comes with a range of new challenges and opportunities.

In keeping up to date with emerging technologies and working collaboratively through strategic partnerships, Health Canada seeks to position itself as a regulator at the forefront of health innovation. Following the targeted sectoral review of the Health and Biosciences Sector Regulatory Review consultation by the Treasury Board Secretariat, Health Canada held a number of targeted meetings with a broad range of stakeholders.

This report outlines the methodologies used to look ahead at the emerging health technology environment, [emphasis mine] the potential areas of focus that resulted, and the key findings from consultations.

… the Department identified the following key drivers that are expected to shape the future of health innovation:

  1. The use of “big data” to inform decision-making: Health systems are generating more data, and becoming reliant on this data. The increasing accuracy, types, and volume of data available in real time enable automation and machine learning that can forecast activity, behaviour, or trends to support decision-making.
  2. Greater demand for citizen agency: Canadians increasingly want and have access to more information, resources, options, and platforms to manage their own health (e.g., mobile apps, direct-to-consumer services, decentralization of care).
  3. Increased precision and personalization in health care delivery: Diagnostic tools and therapies are increasingly able to target individual patients with customized therapies (e.g., individual gene therapy).
  4. Increased product complexity: Increasingly complex products do not fit well within conventional product classifications and standards (e.g., 3D printing).
  5. Evolving methods for production and distribution: In some cases, manufacturers and supply chains are becoming more distributed, challenging the current framework governing production and distribution of health products.
  6. The ways in which evidence is collected and used are changing: The processes around new drug innovation, research and development, and designing clinical trials are evolving in ways that are more flexible and adaptive.

With these key drivers in mind, the Department selected the following six emerging technologies for further investigation to better understand how the health product space is evolving:

  1. Artificial intelligence, including activities such as machine learning, neural networks, natural language processing, and robotics.
  2. Advanced cell therapies, such as individualized cell therapies tailor-made to address specific patient needs.
  3. Big data, from sources such as sensors, genetic information, and social media that are increasingly used to inform patient and health care practitioner decisions.
  4. 3D printing of health products (e.g., implants, prosthetics, cells, tissues).
  5. New ways of delivering drugs that bring together different product lines and methods (e.g., nano-carriers, implantable devices).
  6. Gene editing, including individualized gene therapies that can assist in preventing and treating certain diseases.

Next, to test the drivers identified and further investigate emerging technologies, the Department consulted key organizations and thought leaders across the country with expertise in health innovation. To this end, Health Canada held seven workshops with over 140 representatives from industry associations, small-to-medium sized enterprises and start-ups, larger multinational companies, investors, researchers, and clinicians in Ottawa, Toronto, Montreal, and Vancouver. [emphases mine]

The ‘outocme’ report, ‘What we heard …’, is well worth reading in its entirety; it’s about 9 pp.

I have one comment, ‘stakeholders’ don’t seem to include anyone who isn’t “from industry associations, small-to-medium sized enterprises and start-ups, larger multinational companies, investors, researchers, and clinician” or from “Ottawa, Toronto, Montreal, and Vancouver.” Aren’t the rest of us stakeholders?

Innovating risk analysis

This line in the report caught my eye (from Health Canada’s Toward a strengthened Assisted Human Reproduction Act ; A Consultation with Canadians on Key Policy Proposals webpage),

There is increasing need to enable innovation in a flexible, risk-based way, with appropriate oversight to ensure safety, quality, and efficacy. [emphases mine]

It reminded me of the 2019 federal budget (from my March 22, 2019 posting). One comment before proceeding, regulation and risk are tightly linked and, so, by innovating regulation they are by exttension alos innovating risk analysis,

… Budget 2019 introduces the first three “Regulatory Roadmaps” to specifically address stakeholder issues and irritants in these sectors, informed by over 140 responses [emphasis mine] from businesses and Canadians across the country, as well as recommendations from the Economic Strategy Tables.

Introducing Regulatory Roadmaps

These Roadmaps lay out the Government’s plans to modernize regulatory frameworks, without compromising our strong health, safety, and environmental protections. They contain proposals for legislative and regulatory amendments as well as novel regulatory approaches to accommodate emerging technologies, including the use of regulatory sandboxes and pilot projects—better aligning our regulatory frameworks with industry realities.

Budget 2019 proposes the necessary funding and legislative revisions so that regulatory departments and agencies can move forward on the Roadmaps, including providing the Canadian Food Inspection Agency, Health Canada and Transport Canada with up to $219.1 million over five years, starting in 2019–20, (with $0.5 million in remaining amortization), and $3.1 million per year on an ongoing basis.

In the coming weeks, the Government will be releasing the full Regulatory Roadmaps for each of the reviews, as well as timelines for enacting specific initiatives, which can be grouped in the following three main areas:

What Is a Regulatory Sandbox? Regulatory sandboxes are controlled “safe spaces” in which innovative products, services, business models and delivery mechanisms can be tested without immediately being subject to all of the regulatory requirements.
– European Banking Authority, 2017

Establishing a regulatory sandbox for new and innovative medical products
The regulatory approval system has not kept up with new medical technologies and processes. Health Canada proposes to modernize regulations to put in place a regulatory sandbox for new and innovative products, such as tissues developed through 3D printing, artificial intelligence, and gene therapies targeted to specific individuals. [emphasis mine]

Modernizing the regulation of clinical trials
Industry and academics have expressed concerns that regulations related to clinical trials are overly prescriptive and inconsistent. Health Canada proposes to implement a risk-based approach [emphasis mine] to clinical trials to reduce costs to industry and academics by removing unnecessary requirements for low-risk drugs and trials. The regulations will also provide the agri-food industry with the ability to carry out clinical trials within Canada on products such as food for special dietary use and novel foods.

Does the government always get 140 responses from a consultation process? Moving on, I agree with finding new approaches to regulatory processes and oversight and, by extension, new approaches to risk analysis.

Earlier in this post, I asked if someone had a budget for public relations/promotion. I wasn’t joking. My March 22, 2019 posting also included these line items in the proposed 2019 budget,

Budget 2019 proposes to make additional investments in support of the following organizations:
Stem Cell Network: Stem cell research—pioneered by two Canadians in the 1960s [James Till and Ernest McCulloch]—holds great promise for new therapies and medical treatments for respiratory and heart diseases, spinal cord injury, cancer, and many other diseases and disorders. The Stem Cell Network is a national not-for-profit organization that helps translate stem cell research into clinical applications and commercial products. To support this important work and foster Canada’s leadership in stem cell research, Budget 2019 proposes to provide the Stem Cell Network with renewed funding of $18 million over three years, starting in 2019–20.

Genome Canada: The insights derived from genomics—the study of the entire genetic information of living things encoded in their DNA and related molecules and proteins—hold the potential for breakthroughs that can improve the lives of Canadians and drive innovation and economic growth. Genome Canada is a not-for-profit organization dedicated to advancing genomics science and technology in order to create economic and social benefits for Canadians. To support Genome Canada’s operations, Budget 2019 proposes to provide Genome Canada with $100.5 million over five years, starting in 2020–21. This investment will also enable Genome Canada to launch new large-scale research competitions and projects, in collaboration with external partners, ensuring that Canada’s research community continues to have access to the resources needed to make transformative scientific breakthroughs and translate these discoveries into real-world applications.

Years ago, I managed to find a webpage with all of the proposals various organizations were submitting to a government budget committee. It was eye-opening. You can tell which organizations were able to hire someone who knew the current government buzzwords and the things that a government bureaucrat would want to hear and the organizations that didn’t.

Of course, if the government of the day is adamantly against or uninterested, no amount of persusasion will work to get your organization more money in the budget.

Finally

Reluctantly, I am inclined to explore the topic of emerging technologies such as gene-editing not only in the field of agriculture (for gene-editing of plants, fish, and animals see my November 28, 2018 posting) but also with humans. At the very least, it needs to be discussed whether we choose to participate or not.

If you are interested in the arguments against changing Canada’s prohibition against gene-editing of humans, there’s an Ocotber 2, 2017 posting on Impact Ethics by Françoise Baylis, Professor and Canada Research Chair in Bioethics and Philosophy at Dalhousie University, and Alana Cattapan, Johnson Shoyama Graduate School of Public Policy at the University of Saskatchewan, which makes some compelling arguments. Of course, it was written before the CRISPR twins (my November 28, 2018 posting).

Recaliing CRISPR Therapeutics (mentioned by Gierczak), the company received permission to run clinical trials in the US in October 2018 after the FDA (US Food and Drug Administration) lifted an earlier ban on their trials according to an Oct. 10, 2018 article by Frank Vinhuan for exome,

The partners also noted that their therapy is making progress outside of the U.S. They announced that they have received regulatory clearance in “multiple countries” to begin tests of the experimental treatment in both sickle cell disease and beta thalassemia, …

It seems to me that the quotes around “multiple countries” are meant to suggest doubt of some kind. Generally speaking, company representatives make those kinds of generalizations when they’re trying to pump up their copy. E.g., 50% increase in attendance  but no whole numbers to tell you what that means. It could mean two people attended the first year and then brought a friend the next year or 100 people attended and the next year there were 150.

Despite attempts to declare personalized medicine as having arrived, I think everything is still in flux with no preordained outcome. The future has yet to be determined but it will be and I , for one, would like to have some say in the matter.

Two new Canada Excellence Research Chairs (CERC) at the University of British Columbia (Canada) bring bioproducts and precision medicine skills

This is very fresh news. One of these chairs has not yet been listed (at the time of this writing) as a member of the institute that he will be leading. Here’s the big picture news from an
April 17, 2019 University of British Columbia (UBC) news release, Note: Links have been removed,

Two internationally recognized researchers join the University of British Columbia as Canada Excellence Research Chairs, bringing international talent in the fields of forest bioproducts and precision cancer drug design.

Orlando Rojas has accepted the Canada Excellence Research Chair in Forest Bioproducts, while Sriram Subramaniam will hold the Gobind Khorana Canada Excellence Research Chair in Precision Cancer Drug Design—named after late Nobel Prize-winning UBC biochemistry professor Har Gobind Khorana.

“We are delighted to welcome Dr. Rojas and Dr. Subramaniam to UBC,” said UBC President and Vice-Chancellor, Professor Santa J. Ono. “Thanks to the CERC program and the generous support of our partners, including VGH & UBC Hospital Foundation, we have an opportunity to continue to build on UBC’s reputation as a global leader in these vitally important research fields.”

The Canada Excellence Research Chairs (CERC) program was established by the federal government in 2008 to attract top research talent from abroad to Canada. UBC will receive up to $10 million over seven years to support each chair and their research teams. In addition, a philanthropic gift of $18 million made to VGH & UBC Hospital Foundation will support cancer drug design that will be carried out by Subramaniam in close partnership with UBC and the Vancouver Prostate Centre at VGH.

“VGH & UBC Hospital Foundation is honoured to announce an $18 million gift from Aqueduct Foundation on behalf of an anonymous donor that will increase capacity for discovering and testing new life-saving cancer treatments right here in B.C. This funding will specifically support the design of precise, targeted and cost-effective drugs for cancer in work led by Dr. Sriram Subramaniam in close partnership with UBC and the Vancouver Prostate Centre at VGH and other research centres,” says Barbara Grantham, president and CEO of VGH & UBC Hospital Foundation.

Bioproducts

The April 17, 2019 UBC news release, goes on to describe the two new chairs,

Breaking new ground in forest bioproducts

Orlando Rojas comes to UBC from Aalto University [Finland], where he directs with VTT, the Technical Research Centre of Finland, a scientific cluster to advance the Finnish materials bio-economy. A recipient of the Anselme Payen Award—one of the highest international recognitions in the area of cellulose and renewable materials—and an elected member of the American Chemical Society and the Finnish Academy of Science and Letters, Rojas is recognized as a worldwide leader in the area of nanocelluloses.

“I’m thrilled to join an already stellar team of researchers at UBC’s BioProducts Institute,” said Rojas. “My research is aimed at uncovering solutions that can be found in nature to fulfill our material needs by using sustainably, readily available bio-resources. I hope to break new grounds to create positive societal impacts and to better our quality of life.”

As the CERC in Forest Bioproducts, Rojas will establish a world-class research program in genomics, synthetic biology, materials science and engineering. Together with his team and by applying cutting-edge nano- and biotechnologies, he will discover new strategies to isolate and transform biomass components—non-fossil organic materials derived from plants (including wood)—as well as side-streams and residuals from forestry and agriculture, oils and biomolecules. The work will lead to the generation of new bio-based precursors and advanced materials critical to the future bioeconomy. Rojas will be the scientific director of the UBC BioProducts Institute, synergizing a distinguished group of professors and researchers across campus who will conduct multi- and cross-disciplinary research that will position UBC at the forefront in the area.

As climate change continues to be the greatest threat to our world, the need to transition toward a more sustainable bio-based circular economy is critical. Rojas’ research is vital in understanding the role of forest and other plant-based resources in facilitating the transition to renewable materials and bioproducts.

As I noted earlier, Rojas has yet to be added to the UBC BioProducts Institute roster but I did find a listing of his published papers on Google Scholar and noted a number of them are focused on nanocellulose with at least one study on cellulose nanocrystals (CNC),

  • Cellulose nanocrystals: chemistry, self-assembly, and applications [by] Y Habibi, LA Lucia, OJ Rojas Chemical reviews 110 (6), 3479-3500

The University of British Columbia was the site for much of the early work in Canada and internationally on cellulose nanocrystals. After the provincial government lost interest in supporting it, the researchers at FPInnovations (I think it was a university spin-off organization) moved their main headquarters (leaving a smaller group in British Columbia) to the province of Québec where they receive significant support . In turn, FPInnovations spun-off a company, CelluForce which produces CNC from forest products.This news about Roja’s appointment would seem to make for an interesting development in Canada’s nanocellulose story.

Precision medicine with cryo-electron microscopy

Now for the second CERC appointment, from the April 17, 2019 UBC news release,

Putting Canada at the forefront of precision medicine

Sriram Subramaniam is recognized as a global leader in the emerging field of cryo-electron microscopy, or cryo-EM, a technology that has sparked a revolution in imaging of protein complexes. Subramaniam and his team demonstrated that proteins and protein-bound drugs could be visualized at atomic resolution with cryo-EM, paving the way for this technology to be used in accelerating drug discovery.

Subramaniam comes to UBC’s faculty of medicine from the US National Cancer Institute (NCI) at the National Institutes of Health (NIH) where he led a research team that made seminal advances in molecular and cellular imaging using electron microscopy, including work on advancing vaccine design for viruses such as HIV. Subramaniam is also founding director of the National Cryo-EM Program at NCI, NIH.

As the Gobind Khorana Canada Excellence Research Chair in Precision Cancer Drug Design, Subramaniam will establish and direct a laboratory located at UBC, aimed at bringing about transformative discoveries in cancer, neuroscience and infectious disease. Subramaniam is appointed both in the department of urologic sciences and in biochemistry and molecular biology at UBC, and is linked to the precision cancer drug design program at the Vancouver Prostate Centre at VGH.

His research is supported by a philanthropic gift of $18 million made to VGH & UBC Hospital Foundation. He will work in close partnership with the Vancouver Prostate Centre at VGH.

“We would not be able to undertake this path aimed at leveraging advances in imaging technology to improve patient outcomes if it weren’t for the generous support of the donor, the Canadian government, and VGH & UBC Hospital Foundation,” said Subramaniam. “I am proud to be part of a team of outstanding researchers here in Vancouver, and working together to harness the true potential of cryo-EM to accelerate drug design. Our work has the potential to establish VGH, UBC and Canada at the forefront of the emerging era of precision medicine.”

I was not able to find much in the way of additional information about Subramaniam—other than this (from the High Resolution Electron Microscopy Lab Members webpage),

Sriram Subramaniam received his Ph.D. in Physical Chemistry from Stanford University and completed postdoctoral training in the Departments of Chemistry and Biology at M.I.T. [Massachusetts Institute of Technology] He is chief of the Biophysics Section in the Laboratory of Cell Biology at the Center for Cancer Research, National Cancer Institute. He holds a visiting faculty appointment at the Johns Hopkins University School of Medicine.

Welcome to both Orlando J. Rohas and Sriram Subramaniam!

Alleviating joint damage and inflammation from arthritis with neutrophil nanosponges

Assuming you’d be happy with limiting the damage for rheumatoid arthritis, at some point in the future, this research looks promisin. Right now it appears the researchers aren’t anywhere close to a clinical trial. From a Sept. 3, 2018 news item on ScienceDaily,

Engineers at the University of California San Diego [UCSD] have developed neutrophil “nanosponges” that can safely absorb and neutralize a variety of proteins that play a role in the progression of rheumatoid arthritis. Injections of these nanosponges effectively treated severe rheumatoid arthritis in two mouse models. Administering the nanosponges early on also prevented the disease from developing.

A Sept. 3, 2018 UCSD press release (also on EurekAlert), which originated the news item, provides more detail,

“Nanosponges are a new paradigm of treatment to block pathological molecules from triggering disease in the body,” said senior author Liangfang Zhang, a nanoengineering professor at the UC San Diego Jacobs School of Engineering. “Rather than creating treatments to block a few specific types of pathological molecules, we are developing a platform that can block a broad spectrum of them, and this way we can treat and prevent disease more effectively and efficiently.”

This work is one of the latest examples of therapeutic nanosponges developed by Zhang’s lab. Zhang, who is affiliated with the Institute of Engineering in Medicine and Moores Cancer Center at UC San Diego, and his team previously developed red blood cell nanosponges to combat and prevent MRSA infections and macrophage nanosponges to treat and manage sepsis.

neutrophil nanosponge cartoon
Illustration of a neutrophil cell membrane-coated nanoparticle.

The new nanosponges are nanoparticles of biodegradable polymer coated with the cell membranes of neutrophils, a type of white blood cell.

Neutrophils are among the immune system’s first responders against invading pathogens. They are also known to play a role in the development of rheumatoid arthritis, a chronic autoimmune disease that causes painful inflammation in the joints and can ultimately lead to damage of cartilage and bone tissue.

When rheumatoid arthritis develops, cells in the joints produce inflammatory proteins called cytokines. Release of cytokines signals neutrophils to enter the joints. Once there, cytokines bind to receptors on the neutrophil surfaces, activating them to release more cytokines, which in turn draws more neutrophils to the joints and so on.

The nanosponges essentially nip this inflammatory cascade in the bud. By acting as tiny neutrophil decoys, they intercept cytokines and stop them from signaling even more neutrophils to the joints, reducing inflammation and joint damage.

These nanosponges offer a promising alternative to current treatments for rheumatoid arthritis. Some monoclonal antibody drugs, for example, have helped patients manage symptoms of the disease, but they work by neutralizing only specific types of cytokines. This is not sufficient to treat the disease, said Zhang, because there are so many different types of cytokines and pathological molecules involved.

“Neutralizing just one or two types might not be as effective. So our approach is to take neutrophil cell membranes, which naturally have receptors to bind all these different types of cytokines, and use them to manage an entire population of inflammatory molecules,” said Zhang.

“This strategy removes the need to identify specific cytokines or inflammatory signals in the process. Using entire neutrophil cell membranes, we’re cutting off all these inflammatory signals at once,” said first author Qiangzhe Zhang, a Ph.D. student in Professor Liangfang Zhang’s research group at UC San Diego.

To make the neutrophil nanosponges, the researchers first developed a method to separate neutrophils from whole blood. They then processed the cells in a solution that causes them to swell and burst, leaving the membranes behind. The membranes were then broken up into much smaller pieces. Mixing them with ball-shaped nanoparticles made of biodegradable polymer fused the neutrophil cell membranes onto the nanoparticle surfaces.

“One of the major challenges of this work was streamlining this entire process, from isolating neutrophils from blood to removing the membranes, and making this process repeatable. We spent a lot of time figuring this out and eventually created a consistent neutrophil nanosponge production line,” said Qiangzhe Zhang.

In mouse models of severe rheumatoid arthritis, injecting nanosponges in inflamed joints led to reduced swelling and protected cartilage from further damage. The nanosponges performed just as well as treatments in which mice were administered a high dose of monoclonal antibodies.

The nanosponges also worked as a preventive treatment when administered prior to inducing the disease in another group of mice.

Professor Liangfang Zhang cautions that the nanosponge treatment does not eliminate the disease. “We are basically able to manage the disease. It’s not completely gone. But swelling is greatly reduced and cartilage damage is minimized,” he said.

The team hopes to one day see their work in clinical trials.

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

Neutrophil membrane-coated nanoparticles inhibit synovial inflammation and alleviate joint damage in inflammatory arthritis by Qiangzhe Zhang, Diana Dehaini, Yue Zhang, Julia Zhou, Xiangyu Chen, Lifen Zhang, Ronnie H. Fang, Weiwei Gao, & Liangfang Zhang. Nature Nanotechnology (2018) DOI: https://doi.org/10.1038/s41565-018-0254-4 Published 03 September 2018

This paper is behind a paywall.

Heart and mind: Dr. Paolo Raggi speaks about cardiovascular health and its links to mental health on April 16, 2019 in Vancouver (Canada)

ARPICO, the Embassy of Italy in Ottawa, the Consulate General of Italy in Vancouver, and Paolo Raggi on April 16, 2019, Italian Research Day in the World

I love this image with the brain and heart as plants rooted in the earth for this upcoming ARPICO (Society of Italian Researchers & Professionals in Western Canada) event. I received a March 19, 2019 announcement (via email) from ARPICO about their latest Vancouver event, which is celebrating the 2019 Italian Research Day in the World,

… we are pleased to announce our next event in celebration of Italian Research of the World Day. On April 16th, 2019 at the Italian Cultural Centre, we will have the privilege of hosting the distinguished Dr. Paolo Raggi to present on the topic of mental disorders and cardiovascular health.  Dr. Raggi is a pioneer and luminary in the field of heart health, especially for his approach of considering heart disease not as an isolated condition, but in relation to the health of many other organs, an important one among them being our brain.

This event is organized in collaboration with the Embassy of Italy in Ottawa and with the Consulate General of Italy in Vancouver to celebrate the Italian Research in the World Day, instituted starting in 2018 as part of the Piano Straordinario “Vivere all’Italiana” – Giornata della ricerca Italiana nel mondo. The celebration day was chosen by government decree to be every year on April 15 on the anniversary of the birth of Leonardo da Vinci.

The main objective of the Italian Research Day in the World is to value the quality and competencies of Italian researchers abroad, but also to promote concrete actions and investments to allow Italian researchers to continue pursuing their careers in their homeland. Italy wishes to enable Italian talents to return from abroad as well as to become an attractive environment for foreign researchers.

We look forward to seeing everyone there.
The evening agenda is as follows:
6:30 pm – Doors Open for Registration
7:00 pm – Start of the evening event with introductions & lecture by Dr. Paolo Raggi
~8:00 pm – Q & A Period
to follow – Mingling & Refreshments until about 9:30 pm
If you have not already done so, please register for the event by visiting the EventBrite link or RSVPing to info@arpico.ca.
Further details are also available at arpico.ca and Eventbrite.

Mental Disorders and Cardiovascular Health: A Critical, if Overlooked, Connection
Despite extraordinary advances in the diagnosis and care of heart disease, this ailment continues to affect a very large portion of the North American population and its related costs keep climbing. Reducing morbidity and mortality from heart disease will require a strong and integrated approach involving both research and clinical efforts aimed at prevention of disease rather than delayed care of its advanced complications. Dr. Raggi’s research investigates the mechanisms and prevention of heart disease and includes, among many other facets of this complex condition, the impact of mental stress disorders on coronary artery disease.

Paolo Raggi, MD, is a Professor of Medicine at the University of Alberta in Edmonton, AB and he is the former Director of the Mazankowski Alberta Heart Institute and Chair of Cardiac Research at the University of Alberta, in Edmonton AB, Canada. He is also an Adjunct Professor of Radiology as well as Professor of Population Health and Epidemiology at Emory University in Atlanta, GA, USA.

Dr. Raggi has been involved in research in the following fields: atherosclerosis imaging, vascular calcification, lipid metabolism, cardiovascular disease associated with: chronic kidney disease, rheumatological disorders, HIV infection, diabetes mellitus, the metabolic syndrome and the impact of mental stress disorders on coronary artery disease. He regularly engages in the interpretation of echocardiography, computed tomography, magnetic resonance and nuclear cardiology imaging studies for the diagnosis of coronary artery disease, subclinical atherosclerosis and evaluation of left ventricular function and viability.

He lectured extensively both nationally and internationally and has been a research mentor for numerous trainees. The results of his work have been published in the New England Journal of Medicine, The Lancet, Archives of Internal Medicine, Circulation, Journal of the American College of Cardiology, European Heart Journal, Kidney International, American Journal of Kidney Diseases, Radiology, Chest and several others. He has contributed over 350 publications to major peer-reviewed journals and 30 chapters for books on cardiovascular imaging and preventive cardiology.

Dr. Raggi has received numerous awards as best teaching attending and best clinical investigator nationally and internationally. He serves as a consultant for 30 scientific medical publications, he is Co-Editor of Atherosclerosis, and sits on the Board of 3 peer-reviewed medical journals. He is a fellow of the American College of Physicians, the American College of Cardiology, the American Heart Association, the Canadian Cardiovascular Society, the American Society of Nuclear Cardiology and the Society of Cardiac Computed Tomography of which he was a co-founder. Dr. Raggi received the highest honours from the President of Italy in October 2017 and was named Knight of the Order of Stars, typically bestowed upon Italian citizens who have distinguished themselves for their service to the Country of origin and/or adoptive countries.
 
WHEN: Tuesday, April 16th, 2019 at 7:00pm (doors open at 6:30pm)
WHERE: Italian Cultural Centre – Museum & Art Gallery – 3075 Slocan St, Vancouver, BC, V5M 3E4
RSVP: Please RSVP at EventBrite (https://mentaldisorderscardiovascularhealth.eventbrite.ca) or email info@arpico.ca
 
Tickets are Needed
Tickets are FREE, but all individuals are requested to obtain “free-admission” tickets on EventBrite site due to limited seating at the venue. Organizers need accurate registration numbers to manage wait lists and prepare name tags.

All ARPICO events are 100% staffed by volunteer organizers and helpers, however, room rental, stationery, and guest refreshments are costs incurred and underwritten by members of ARPICO. Therefore to be fair, all audience participants are asked to donate to the best of their ability at the door or via EventBrite to “help” defray costs of the event.
 
FAQs
Where can I contact the organizer with any questions? info@arpico.ca
Do I have to bring my printed ticket to the event? No, you do not. Your name will be on our Registration List at the Check-in Desk.
Is my registration/ticket transferrable? If you are unable to attend, another person may use your ticket. Please send us an email at info@arpico.ca of this substitution to correct our audience Registration List and to prepare guest name tags.
Can I update my registration information? Yes. If you have any questions, contact us at info@arpico.ca
I am having trouble using EventBrite and cannot reserve my ticket(s). Can someone at ARPICO help me with my ticket reservation? Of course, simply send your ticket request to us at info@arpico.ca so we help you.
 
What are my transport/parking options?
Bus/Train: The Millenium Line Renfrew Skytrain station is a 5 minute walk from the Italian Cultural Centre.
Parking: Free Parking is vastly available at the ICC’s own parking lot.

I’m a sucker for any reference to the ancient Romans, which can be found on the event announcement on ARPICO’s homepage and on the EventBrite registration page for the event,

The ancient Romans believed that a healthy body and mind go hand in hand: mens sana in corpore sano! During the American Civil War physicians described the Soldier’s Heart as a syndrome that occurred on the battlefield that involved symptoms very similar to modern day posttraumatic stress disorder (PTSD). They also noted that these soldiers manifested exaggerated cardiovascular reactivity and “abnormalities of the heart”. Interventions were developed to reduce the damage on the cardiovascular system and included surgical interventions to neutralize the sympathetic nervous system hyper-activity. With the advent of modern psychoanalysis, psychiatric symptoms became divorced from the body and were re-located to unconscious systems.

More recently, advancements in psychosomatic medicine and related fields clarified the complexity of the interaction between central and peripheral nervous system disorders, inflammation and cardiovascular diseases. This field of research has witnessed a quick expansion that brought to the discovery of important mechanisms of cardiovascular disease and potential therapeutic advances.

Happy Italian Research Day in the World (Giornata della ricerca Italiana nel mondo) which is held on April 15, 2019 (da Vinci’s birthday) as noted in the ARPICO announcement! If you’re planning to attend, don’t forget to register for Dr. Raggi’s talk at EventBrite (https://mentaldisorderscardiovascularhealth.eventbrite.ca) or email info@arpico.ca.

Human lung enzyme can degrade graphene

Caption: A human lung enzyme can biodegrade graphene. Credit: Fotolia Courtesy: Graphene Flagship

The big European Commission research programme, Grahene Flagship, has announced some new work with widespread implications if graphene is to be used in biomedical implants. From a August 23, 2018 news item on ScienceDaily,

Myeloperoxidase — an enzyme naturally found in our lungs — can biodegrade pristine graphene, according to the latest discovery of Graphene Flagship partners in CNRS, University of Strasbourg (France), Karolinska Institute (Sweden) and University of Castilla-La Mancha (Spain). Among other projects, the Graphene Flagship designs based like flexible biomedical electronic devices that will interfaced with the human body. Such applications require graphene to be biodegradable, so our body can be expelled from the body.

An August 23, 2018 Grapehene Flagship press release (mildly edited version on EurekAlert), which originated the news item, provides more detail,

To test how graphene behaves within the body, researchers analysed how it was broken down with the addition of a common human enzyme – myeloperoxidase or MPO. If a foreign body or bacteria is detected, neutrophils surround it and secrete MPO, thereby destroying the threat. Previous work by Graphene Flagship partners found that MPO could successfully biodegrade graphene oxide.

However, the structure of non-functionalized graphene was thought to be more resistant to degradation. To test this, the team looked at the effects of MPO ex vivo on two graphene forms; single- and few-layer.

Alberto Bianco, researcher at Graphene Flagship Partner CNRS, explains: “We used two forms of graphene, single- and few-layer, prepared by two different methods in water. They were then taken and put in contact with myeloperoxidase in the presence of hydrogen peroxide. This peroxidase was able to degrade and oxidise them. This was really unexpected, because we thought that non-functionalized graphene was more resistant than graphene oxide.”

Rajendra Kurapati, first author on the study and researcher at Graphene Flagship Partner CNRS, remarks how “the results emphasize that highly dispersible graphene could be degraded in the body by the action of neutrophils. This would open the new avenue for developing graphene-based materials.”

With successful ex-vivo testing, in-vivo testing is the next stage. Bengt Fadeel, professor at Graphene Flagship Partner Karolinska Institute believes that “understanding whether graphene is biodegradable or not is important for biomedical and other applications of this material. The fact that cells of the immune system are capable of handling graphene is very promising.”

Prof. Maurizio Prato, the Graphene Flagship leader for its Health and Environment Work Package said that “the enzymatic degradation of graphene is a very important topic, because in principle, graphene dispersed in the atmosphere could produce some harm. Instead, if there are microorganisms able to degrade graphene and related materials, the persistence of these materials in our environment will be strongly decreased. These types of studies are needed.” “What is also needed is to investigate the nature of degradation products,” adds Prato. “Once graphene is digested by enzymes, it could produce harmful derivatives. We need to know the structure of these derivatives and study their impact on health and environment,” he concludes.

Prof. Andrea C. Ferrari, Science and Technology Officer of the Graphene Flagship, and chair of its management panel added: “The report of a successful avenue for graphene biodegradation is a very important step forward to ensure the safe use of this material in applications. The Graphene Flagship has put the investigation of the health and environment effects of graphene at the centre of its programme since the start. These results strengthen our innovation and technology roadmap.”

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

Degradation of Single‐Layer and Few‐Layer Graphene by Neutrophil Myeloperoxidase by Dr. Rajendra Kurapati, Dr. Sourav P. Mukherjee, Dr. Cristina Martín, Dr. George Bepete, Prof. Ester Vázquez, Dr. Alain Pénicaud, Prof. Dr. Bengt Fadeel, Dr. Alberto Bianco. Angewandte Chemie https://doi.org/10.1002/anie.201806906 First published: 13 July 2018

This paper is behind a paywall.

A sprinkling of science and art/science events in Vancouver (Canada) during February and March 2019)

One February event previously mentioned in my February 4, 2019 posting, ‘Heart & Art—the first Anatomy Night in Canada—February 14, 2019 in Vancouver’, is sold out! If you’re feeling lucky, you could join the waitlist (click on Tickets). I think the University of British Columbia’s Heartfelt images created by medical students will be featured at the event. The image below is from Heartfelt Images 2013,

Turbulent Flow; 1st Place Credit: April Lu (VFMP)

I love how the artist has integrated a salmon and Hokusai’s Great Wave, while conveying information about blood flow into and out of the heart. BTW, you might want to look at the image on its ‘homesite’ as I don’t think the aspect ratio here is quite right. Note: Heartfelt Images were copied and moved to a new website and organized with newer images into the teachingmedicine.com site’s ‘Art Gallery‘.

Onwards, I have two events and an opportunity.

Traumatic Brain Injury: a Brain Talks event

Courtesy: Brain Talks

The Brain Talks folks at the University of British Columbia (UBC) emailed a February 8, 2019 announcement (Note: I have made a few minor formatting changes to the following),

Traumatic Brain Injury; Molecular Mechanisms to Chronic Care

Wednesday, February 20th, 2019 from 6:00 pm – 8:30 pm

Join us on February 20th for talks on Traumatic Brain Injury spanning from molecular mechanisms to chronic clinical care. We are excited to announce presenters who both practice in the community and perform high level research. Our presenters include Dr. Cheryl Wellington, director of ABI Wellness Mark Watson, and clinical rehabilitation director Heather Branscombe.

Dr. Cheryl Wellington is a professor and researcher internationally recognized for her work on lipid and lipoprotein metabolism in the brain. Her group has made key contributions to the understanding of the role of apolipoprotein E (apoE) in Alzheimer’s Disease as well as the critical role played in repair of damaged neurons after TBI.

Mark Watson is the Chief Executive Officer of ABI Wellness, a clinic specializing in providing services for patients with chronic brain injury to improve higher order cognitive functioning. Mark has worked in education and cognitive rehabilitation since 2002, having served as a teacher, administrator, Executive Director and CEO. A frequent speaker on the topic of brain injury rehabilitation Mark has presented this work to: Public health agencies, BC Cancer Agency, The NHL Alumni Assoc., NFLPA Washington State.

Heather Branscombe serves as the Clinic Director and owner of Abilities Neurological Rehabilitation. A physiotherapist by training, Heather has consulted as a clinical specialist to a rehabilitation technology company and has taught therapists, orthotists and physicians across Canada. She is involved in research projects with the University of British Columbia (FEATHER’s project) and has been asked to be the exclusive BC provider of emerging therapy practice such as the telemedicine driven ReJoyce through rehabtronics. Professionally, Heather volunteers her time as a member of the Board of Directors for the Stroke Recovery Association of B.C. and is the past-chair of the Neurosciences Division of the Canadian Physiotherapy Association.

After the talk, at 7:30 pm, we host a social gathering with healthy food and non-alcoholic drinks. For physicians, the event is CME accredited for a MOC credit of 1.5.

We look forward to seeing you there!

Should you be interested in attending, tickets are $10 + tax. Here are the logistics (from the Traumatic Brain Injury event webpage),

Date and Time
Wed, 20 February 2019
6:00 PM – 8:00 PM PST
Add to Calendar
Location
Paetzhold Theater
Vancouver General Hospital
Vancouver, BC
View Map
Refund Policy
Refunds up to 1 day before event

You can purchase a ticket by going to the Traumatic Brain Injury event webpage.

Linguistics is a social science

I don’t offer much coverage of the social sciences, so there’s this to partially make up for it. From a February 7, 2019 Society of Italian Researchers and Professionals in Western Canada (ARPICO) announcement (received via email),

We are pleased to be writing to you to announce the first event of 2019. After having learned how hard-core dark matter physicists are finding out what our universe is made of, we’ll next have the pleasure to hear from a scholar in a humanistic discipline. Mark Turin will be talking on the topic of language diversity and its importance in our time. In a city with some of the highest levels of cultural variety in the nation, we believe this topic is very relevant and timely. Please, read on for details on the lecture by Dr. Turin in a few weeks.

The first event of ARPICO’s winter 2019 activity will take place on Wednesday, March 6th, 2019 at the Italian Cultural Centre (see the attached map for parking and location). Our speaker will be Dr. Mark Turin, an Associate Professor of Anthropology and First Nations Languages at the University of British Columbia in Vancouver. Trained in anthropology and linguistics, he has worked in collaborative partnership with Indigenous peoples in the Himalayas for over 20 years and more recently with First Nations communities in the Pacific Northwest. He is a committed advocate for the enduring role of Indigenous and minority languages, online, in print and on air through his BBC radio series.

We look forward to seeing everyone there.
The evening agenda is as follows:
6:30 pm – Doors Open for Registration
7:00 pm – Introduction by Nicola Fameli and Lucio Sacchetti
7:15 pm – Start of the evening event with introductions & lecture by Dr. Mark Turin
~8:00 pm – Q & A Period
to follow – Mingling & Refreshments until about 9:30 pm
If you have not already done so, please register for the event by visiting the EventBrite link or RSVPing to info@arpico.ca.
..

Also included in the announcement is more detail about the March 6, 2019 talk along with some logistical information,

Rising Voices: Linguistic diversity in a Globalized World

The linguistic diversity of our species is under extreme stress, as are the communities who speak increasingly endangered speech forms. Of the world’s living languages, currently numbering around 7,000, around half will cease to be spoken as everyday vernaculars by the end of this century.

For communities around the world, local languages function as vehicles for the transmission of unique traditional knowledge and cultural heritage that become threatened when elders die and livelihoods are disrupted. As globalisation and rapid socio-economic change exert complex pressures on smaller communities, cultural and linguistic diversity is being transformed through assimilation to more dominant ways of life.

In 2016, the United Nations General Assembly adopted a resolution proclaiming 2019 as the International Year of Indigenous Languages to help promote and protect Indigenous languages. This celebration of linguistic vitality and resilience is welcome, but is it enough? And in an increasingly and often uncomfortably interconnected world, what is the role for the ‘heritage’ languages that migrants bring with them when they move and settle in new places?

In this richly illustrated lecture, I will draw on contemporary examples from North America, Asia and Europe to explore the enduring importance and compelling value of linguistic diversity in the 21st century.
 
WHEN: Wednesday, March 6th, 2019 at 7:00pm (doors open at 6:30pm)
WHERE:Italian Cultural Centre – Museum & Art Gallery – 3075 Slocan St, Vancouver, BC, V5M 3E4
RSVP: Please RSVP at EventBrite (https://linguisticdiversity.eventbrite.ca/) or email info@arpico.ca

Tickets are Needed
Tickets are FREE, but all individuals are requested to obtain “free-admission” tickets on EventBrite site due to limited seating at the venue. Organizers need accurate registration numbers to manage wait lists and prepare name tags.

All ARPICO events are 100% staffed by volunteer organizers and helpers, however, room rental, stationery, and guest refreshments are costs incurred and underwritten by members of ARPICO. Therefore to be fair, all audience participants are asked to donate to the best of their ability at the door or via EventBrite to “help” defray costs of the event.

Should you attend, read the parking signs carefully. Not all the areas adjacent (that includes parts of the parking lot) to the Italian Cultural Centre are open to public parking.

Her Story: an art/sci opportunity for filmmakers and scientists in Metro Vancouver

I found this on the Curiosity Collider website (Note: I have made a few minor formatting changes),

Her Story: Canadian Women Scientists will be a series of artist-created narrative videos in which local women scientists tell us stories of Canadian women who came before them in their field of study.  Through these stories, we will also learn about the narrating scientists themselves. We are looking for several filmmakers to each create one 5 – 6 minute short film that features a mixture of live action, animation, and narration.  Download this call in pdf

Each film is a collaboration between a film artist and a scientist.  The final product will be a storytelling artwork rather than a documentary style presentation.  We encourage teams to incorporate unique complementary visuals that will enhance the scientist’s story and bring it to life.

Filmmakers are submitting an application to work with a scientist, and after being paired with one by Curiosity Collider, the scientist and filmmaker will choose a historical figure and create the content for the film in collaboration.  Filmmakers may indicate a scientific field of interest, or propose their own Canadian woman scientist who would be interested in participating, however overall scientists will be selected with consideration for diversity of subject matter.  Deadline for submission is 25 March 2019.

Your film will premiere as part of this project at an in-person viewing event in a Vancouver theatre in September 2019.  The event will include an interactive component such as a panel discussion on art, science, and gender.  After the premiere event, the videos will be available through Curiosity Colllider’s social media channels including YouTube and our website(s).  We will also pursue subsequent opportunities as they arise, such as film festivals, University screenings, and Women in Science conferences. We envision this first series as the beginning of a collection that we will promote and grow over several years. This is an opportunity to get involved early, to join our growing community, and to be paid for your work.  

We are expecting concept-driven independent freelancers with experience in directing, cinematography, shooting, editing, and animating of short films.  $1300 is allocated to each film, which must feature live action, animation, and narration. Filmmakers are welcome to propose independent work or collaborative work (as a filmmaking team).   If submitting a proposal as a team, the proposal must clarify team member responsibility and breakdown of fee; a team leader who will be responsible for contract and distribution of funds must be specified.  The fee will be paid out only upon completion of the film. There is no additional funding for equipment rental.

Any animation style will be considered.  The following National Film Board examples show a combination of live action, animation, and narration:  
1.  https://bit.ly/2xJTAwz,  2. https://bit.ly/2DDqvbw.  
And this YouTube example shows another animation style (although it is lacking the narration and should be considered a visual example only):  
3.  https://youtu.be/I62CwxUKuGA?t=54
Animation styles not shown in the examples are welcome.  If you have any questions please contact submissions@curiositycollider.org.
All complete submissions will be reviewed and considered.  We will add you to our database of creators and contact you if we feel you are a great fit for any of our other events

Eligibility:
Your submitted materials must fit within our mandate.
You may submit applications for other Collider projects in addition to this one.  
Applications will be accepted from everywhere, however filming will take place in Metro Vancouver, BC.  At this time we are unable to cover travel expenses

In your submission package (scroll down to access submission form), include:
A statement (500 word max) about how you will approach collaboration with the scientist. Tell us about your scientific fields of interest, inspirations, and observations. Include information about your team if applicable.
A bio (200 word max)
A CV (3 page max)
Submit a link to a single video or reel of up to 7 minutes total to represent your work
A list of works included in your video submission, and any brief pertinent details (1 page max)
A link to your website
Your name, address, email, and any other contact information.
If you have any questions about this call for submissions, contact us at submissions@curiositycollider.org.
 
This project is funded by:
Westcoast Women in Engineering and Science (WWEST) and eng•cite The Goldcrop Professorship for Women in Engineering at the University of British Columbia

Enjoy and good luck!

“Nano-submarines” for a headache

How did those German scientists miss an opportunity to mention the 1966 movie “Fantastic Voyage” and Raquel Welch (the bombshell of her day)? For anyone not familiar with the movie it, featured a submarine that the scientists entered before being miniaturized and …

Raquel Welch, Stephen Boyd, and Arthur Kennedy in Fantastic Voyage (1966) [It looks like the scientists in thesubmarine are now gazing at some body part or other.]

I’m not sure what part of the body these actors are supposed to be dealing with but perhaps this plot description from the IMDB Fantastic Voyage entry will help a bit,

A scientist is nearly assassinated. In order to save him, a submarine is shrunken to microscopic size and injected into his blood stream with a small crew. Problems arise almost as soon as they enter the bloodstream.

Scientist Jan Benes, who knows the secret to keeping soldiers shrunken for an indefinite period, escapes from behind the Iron Curtain with the help of CIA agent Grant. While being transferred, their motorcade is attacked. Benes strikes his head, causing a blood clot to form in his brain. Grant is ordered to accompany a group of scientists as they are miniaturized. The crew has one hour to get in Benes’s brain, remove the clot and get out. Written by Brian Washington <Sargebri@att.net>

Perhaps they’ve left their submarine to get closer to the clot in the brain?

Now for the latest involving “nano-submarines,” or as these scientists prefer nanocarriers, from a July 19, 2018 news item on Nanowerk,

Scientists at the Mainz University Medical Center and the Max Planck Institute for Polymer Research (MPI-P) have developed a new method to enable miniature drug-filled nanocarriers to dock on to immune cells, which in turn attack tumors. In the future, this may lead to targeted treatment that can largely eliminate damage to healthy tissue.

A July 19, 2018 Johannes Gutenberg Universitaet Mainz press release, which originated the news item, explains further,

In modern medicine, patients receiving medication to treat tumors or for pain therapy are often given drugs that disperse throughout the entire body, even though the section of the organ to be treated may be only small and clearly demarcated. One solution would be to administer drugs that target specific cell types. Such nanocarriers are just what scientists are working to develop. These contain, in a manner of speaking, miniature submarines [emphasis mine] no larger than a thousandth of the diameter of a human hair. Invisible to the naked eye, these nanocarriers are loaded with a pharmacologically-active agent, allowing them to function as concentrated transport containers. The surface of these nanocarriers or drug capsules is specially coated to enable them, for example, to dock on to tissue interspersed with tumor cells. The coating is usually composed of antibodies that act much like address labels to seek out binding sites on the target cells, such as tumor cells or immune cells that attack tumors.

Professor Volker Mailänder and his team from the Department of Dermatology at the University Medical Center of Johannes Gutenberg University Mainz (JGU) have recently developed an ingenious new method of binding antibodies to such drug capsules. “Up to now, we have always had to use elaborate chemical methods to bind these antibodies to nanocapsules,” explained Mailänder. “We have now been able to show that all that you need to do is to combine antibodies and nanocapsules together in an acidified solution.”

In their paper in Nature Nanotechnology, the researchers emphasize that binding nanocapsules and antibodies in this way is almost twice as efficient as chemical bonding in the test tube, significantly improving the targeted transport of drugs. In conditions such as those found in the blood, they also found that chemically coupled antibodies almost completely lost their efficacy, while antibodies that are not chemically attached remained functional.

“The standard method of binding antibodies using complex chemical processes can degrade antibodies or even destroy them, or the nanocarrier in the blood can become rapidly covered with proteins,” explained Professor Katharina Landfester from the Max Planck Institute for Polymer Research. In contrast, the new method, which is based on the physical effect known as adsorption or adhesion, protects the antibodies. This makes the nanocarrier more stable and enables it to distribute the drugs more effectively in the body.

To develop their new method, the researchers combined antibodies and drug transporters in an acidic solution. This led – in contrast to binding at a neutral pH – to more efficient coating of the nanoparticle surface. As the researchers explain, this leaves less room on the nanocarrier for blood proteins that could prevent them from docking to a target cell.

Overall, the researchers are confident that the newly developed method will facilitate and improve the efficiency and applicability of therapy methods based on nanotechnology.

I love this video,

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

Pre-adsorption of antibodies enables targeting of nanocarriers despite a biomolecular corona by Manuel Tonigold, Johanna Simon, Diego Estupiñán, Maria Kokkinopoulou, Jonas Reinholz, Ulrike Kintzel, Anke Kaltbeitzel, Patricia Renz, Matthias P. Domogalla, Kerstin Steinbrink, Ingo Lieberwirth, Daniel Crespy, Katharina Landfester & Volker Mailänder. Nature Nanotechnology (2018) DOI: https://doi.org/10.1038/s41565-018-0171-6 Published 18 June 2018

This paper is behind a paywall.