Category Archives: medicine

Sticky-flares nanotechnology to track and observe RNA (ribonucleic acid) regulation

I like the name ‘sticky-flares’ and had hoped there was an amusing story about its origins. Ah well, perhaps I’ll have better luck next time.

This work comes out of Chad Mirkin’s lab at Northwestern University (Chicago, US) according to a July 21, 2015 news item on Azonano,

RNA [ribonucleic acid] is a fundamental ingredient in all known forms of life — so when RNA goes awry, a lot can go wrong. RNA misregulation plays a critical role in the development of many disorders, such as mental disability, autism and cancer.

A new technology — called “Sticky-flares” — developed by nanomedicine experts at Northwestern University offers the first real-time method to track and observe the dynamics of RNA distribution as it is transported inside living cells.

A July 20, 2015 Northwestern University news release by Erin Spain, which originated the news item, describes the research in a little more detail also including information about predecessor technology,

Sticky-flares have the potential to help scientists understand the complexities of RNA better than any analytical technique to date and observe and study the biological and medical significance of RNA misregulation.

Previous technologies made it possible to attain static snapshots of RNA location, but that isn’t enough to understand the complexities of RNA transport and localization within a cell. Instead of analyzing snapshots of RNA to try to understand functioning, Sticky-flares help create an experience that is more like watching live-streaming video.

“This is very exciting because much of the RNA in cells has very specific quantities and localization, and both are critical to the cell’s function, but until this development it has been very difficult, and often impossible, to probe both attributes of RNA in a live cell,” said Chad A. Mirkin, a nanomedicine expert and corresponding author of the study. “We hope that many more researchers will be able to use this platform to increase our understanding of RNA function inside cells.”

Sticky-flares are tiny spherical nucleic acid gold nanoparticle conjugates that can enter living cells and target and transfer a fluorescent reporter or “tracking device” to RNA transcripts. This fluorescent labeling can be tracked via fluorescence microscopy as it is transported throughout the cell, including the nucleus.

In the … paper, the scientists explain how they used Sticky-flares to quantify β–actin mRNA in HeLa cells (the oldest and most commonly used human cell line) as well as to follow the real-time transport of β–actin mRNA in mouse embryonic fibroblasts.

Sticky-flares are built upon another technology from Mirkin’s group called NanoFlares, which was the first genetic-based approach that is able to detect live circulating tumor cells out of the complex matrix that is human blood.

NanoFlares have been very useful for researchers that operate in the arena of quantifying gene expression. AuraSense, Inc., a biotechnology company that licensed the NanoFlare technology from Northwestern University, and EMD-Millipore, another biotech company, have commercialized NanoFlares. There are now more than 1,700 commercial forms of NanoFlares sold under the SmartFlareä name in more than 230 countries.

The Sticky-flare is designed to address limitations of SmartFlares, most notably their inability to track RNA location and enter the nucleus. The Northwestern team believes Sticky-flares are poised to become a valuable tool for researchers who desire to understand the function of RNA in live cells.

Based on the paragraph about the precursor technology’s commercial success , I gather they are excited about similar possibilities for sticky-flares.

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

Quantification and real-time tracking of RNA in live cells using Sticky-flares by William E. Briley, Madison H. Bondy, Pratik S. Randeria, Torin J. Dupper, and Chad A. Mirkin. Published online before print July 20, 2015, doi: 10.1073/pnas.1510581112 PNAS July 20, 2015

This paper is behind a paywall.

On the verge of controlling neurons by wireless?

Scientists have controlled a mouse’s neurons with a wireless device (and unleashed some paranoid fantasies? well, mine if no one else’s) according to a July 16, 2015 news item on Nanowerk (Note: A link has been removed),

A study showed that scientists can wirelessly determine the path a mouse walks with a press of a button. Researchers at the Washington University School of Medicine, St. Louis, and University of Illinois, Urbana-Champaign, created a remote controlled, next-generation tissue implant that allows neuroscientists to inject drugs and shine lights on neurons deep inside the brains of mice. The revolutionary device is described online in the journal Cell (“Wireless Optofluidic Systems for Programmable In Vivo Pharmacology and Optogenetics”). Its development was partially funded by the [US] National Institutes of Health [NIH].

The researchers have made an image/illustration of the probe available,

Mind Bending Probe Scientists used soft materials to create a brain implant a tenth the width of a human hair that can wirelessly control neurons with lights and drugs. Courtesy of Jeong lab, University of Colorado Boulder.

A July 16, 2015 US NIH National Institute of Neurological Disorders and Stroke news release, which originated the news item, describes the study and notes that instructions for building the implant are included in the published study,

“It unplugs a world of possibilities for scientists to learn how brain circuits work in a more natural setting.” said Michael R. Bruchas, Ph.D., associate professor of anesthesiology and neurobiology at Washington University School of Medicine and a senior author of the study.

The Bruchas lab studies circuits that control a variety of disorders including stress, depression, addiction, and pain. Typically, scientists who study these circuits have to choose between injecting drugs through bulky metal tubes and delivering lights through fiber optic cables. Both options require surgery that can damage parts of the brain and introduce experimental conditions that hinder animals’ natural movements.

To address these issues, Jae-Woong Jeong, Ph.D., a bioengineer formerly at the University of Illinois at Urbana-Champaign, worked with Jordan G. McCall, Ph.D., a graduate student in the Bruchas lab, to construct a remote controlled, optofluidic implant. The device is made out of soft materials that are a tenth the diameter of a human hair and can simultaneously deliver drugs and lights.

“We used powerful nano-manufacturing strategies to fabricate an implant that lets us penetrate deep inside the brain with minimal damage,” said John A. Rogers, Ph.D., professor of materials science and engineering, University of Illinois at Urbana-Champaign and a senior author. “Ultra-miniaturized devices like this have tremendous potential for science and medicine.”

With a thickness of 80 micrometers and a width of 500 micrometers, the optofluidic implant is thinner than the metal tubes, or cannulas, scientists typically use to inject drugs. When the scientists compared the implant with a typical cannula they found that the implant damaged and displaced much less brain tissue.

The scientists tested the device’s drug delivery potential by surgically placing it into the brains of mice. In some experiments, they showed that they could precisely map circuits by using the implant to inject viruses that label cells with genetic dyes. In other experiments, they made mice walk in circles by injecting a drug that mimics morphine into the ventral tegmental area (VTA), a region that controls motivation and addiction.

The researchers also tested the device’s combined light and drug delivery potential when they made mice that have light-sensitive VTA neurons stay on one side of a cage by commanding the implant to shine laser pulses on the cells. The mice lost the preference when the scientists directed the device to simultaneously inject a drug that blocks neuronal communication. In all of the experiments, the mice were about three feet away from the command antenna.

“This is the kind of revolutionary tool development that neuroscientists need to map out brain circuit activity,” said James Gnadt, Ph.D., program director at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS).  “It’s in line with the goals of the NIH’s BRAIN Initiative.”

The researchers fabricated the implant using semi-conductor computer chip manufacturing techniques. It has room for up to four drugs and has four microscale inorganic light-emitting diodes. They installed an expandable material at the bottom of the drug reservoirs to control delivery. When the temperature on an electric heater beneath the reservoir rose then the bottom rapidly expanded and pushed the drug out into the brain.

“We tried at least 30 different prototypes before one finally worked,” said Dr. McCall.

“This was truly an interdisciplinary effort,” said Dr. Jeong, who is now an assistant professor of electrical, computer, and energy engineering at University of Colorado Boulder. “We tried to engineer the implant to meet some of neurosciences greatest unmet needs.”

In the study, the scientists provide detailed instructions for manufacturing the implant.

“A tool is only good if it’s used,” said Dr. Bruchas. “We believe an open, crowdsourcing approach to neuroscience is a great way to understand normal and healthy brain circuitry.”

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

Wireless Optofluidic Systems for Programmable In Vivo Pharmacology and Optogenetics by Jae-Woong Jeong, Jordan G. McCall, Gunchul Shin, Yihui Zhang, Ream Al-Hasani, Minku Kim, Shuo Li, Joo Yong Sim, Kyung-In Jang, Yan Shi, Daniel Y. Hong, Yuhao Liu, Gavin P. Schmitz, Li Xia, Zhubin He, Paul Gamble, Wilson Z. Ray, Yonggang Huang, Michael R. Bruchas, and John A. Rogers.  Cell, July 16, 2015. DOI: 10.1016/j.cell.2015.06.058

This paper is behind a paywall.

I last wrote about wireless activation of neurons in a May 28, 2014 posting which featured research at the University of Massachusetts Medical School.

Greening silver nanoparticles with lignin

A July 13, 2015 news item on phys.org highlights a new approach to making silver nanoparticles safer in the environment,

North Carolina State University researchers have developed an effective and environmentally benign method to combat bacteria by engineering nanoscale particles that add the antimicrobial potency of silver to a core of lignin, a ubiquitous substance found in all plant cells. The findings introduce ideas for better, greener and safer nanotechnology and could lead to enhanced efficiency of antimicrobial products used in agriculture and personal care.

A July 13, 2015 North Carolina State University (NCSU) news release (also on EurekAlert), which originated the news item, adds a bit more information,

As the nanoparticles wipe out the targeted bacteria, they become depleted of silver. The remaining particles degrade easily after disposal because of their biocompatible lignin core, limiting the risk to the environment.

“People have been interested in using silver nanoparticles for antimicrobial purposes, but there are lingering concerns about their environmental impact due to the long-term effects of the used metal nanoparticles released in the environment,” said Velev, INVISTA Professor of Chemical and Biomolecular Engineering at NC State and the paper’s corresponding author. “We show here an inexpensive and environmentally responsible method to make effective antimicrobials with biomaterial cores.”

The researchers used the nanoparticles to attack E. coli, a bacterium that causes food poisoning; Pseudomonas aeruginosa, a common disease-causing bacterium; Ralstonia, a genus of bacteria containing numerous soil-borne pathogen species; and Staphylococcus epidermis, a bacterium that can cause harmful biofilms on plastics – like catheters – in the human body. The nanoparticles were effective against all the bacteria.

The method allows researchers the flexibility to change the nanoparticle recipe in order to target specific microbes. Alexander Richter, the paper’s first author and an NC State Ph.D. candidate who won a 2015 Lemelson-MIT prize, says that the particles could be the basis for reduced risk pesticide products with reduced cost and minimized environmental impact.

“We expect this method to have a broad impact,” Richter said. “We may include less of the antimicrobial ingredient without losing effectiveness while at the same time using an inexpensive technique that has a lower environmental burden. We are now working to scale up the process to synthesize the particles under continuous flow conditions.”

I don’t quite understand how the silver nanoparticles/ions are rendered greener. I gather the lignin is harmless but where do the silver nanoparticles/ions go after they’ve been stripped of their lignin cover and have killed the bacteria? I did try reading the paper’s abstract (not much use for someone with my science level),

Silver nanoparticles have antibacterial properties, but their use has been a cause for concern because they persist in the environment. Here, we show that lignin nanoparticles infused with silver ions and coated with a cationic polyelectrolyte layer form a biodegradable and green alternative to silver nanoparticles. The polyelectrolyte layer promotes the adhesion of the particles to bacterial cell membranes and, together with silver ions, can kill a broad spectrum of bacteria, including Escherichia coli, Pseudomonas aeruginosa and quaternary-amine-resistant Ralstonia sp. Ion depletion studies have shown that the bioactivity of these nanoparticles is time-limited because of the desorption of silver ions. High-throughput bioactivity screening did not reveal increased toxicity of the particles when compared to an equivalent mass of metallic silver nanoparticles or silver nitrate solution. Our results demonstrate that the application of green chemistry principles may allow the synthesis of nanoparticles with biodegradable cores that have higher antimicrobial activity and smaller environmental impact than metallic silver nanoparticles.

If you can explain what happens to the silver nanoparticles, please let me know.

Meanwhile, here’s a link to and a citation for the paper,

An environmentally benign antimicrobial nanoparticle based on a silver-infused lignin core by Alexander P. Richter, Joseph S. Brown, Bhuvnesh Bharti, Amy Wang, Sumit Gangwal, Keith Houck, Elaine A. Cohen Hubal, Vesselin N. Paunov, Simeon D. Stoyanov, & Orlin D. Velev. Nature Nanotechnology (2015) doi:10.1038/nnano.2015.141 Published online 13 July 2015

This paper is behind a paywall.

Kill bacterial biofilms and activate healing with cinnamon and peppermint

These compounds based on peppermint and cinnamon kill infection (bacterial biofilm) while helping the wound to heal according to a July 8, 2015 news item on ScienceDaily,

Infectious colonies of bacteria called biofilms that develop on chronic wounds and medical devices can cause serious health problems and are tough to treat. But now scientists have found a way to package antimicrobial compounds from peppermint and cinnamon in tiny capsules that can both kill biofilms and actively promote healing. The researchers say the new material could be used as a topical antibacterial treatment and disinfectant.

A July 8, 2015 American Chemical Society news release on EurekAlert, which originated the news item, provides more detail,

Many bacteria clump together in sticky plaques in a way that makes them difficult to eliminate with traditional antibiotics. Doctors sometimes recommend cutting out infected tissues. This approach is costly, however, and because it’s invasive, many patients opt out of treatment altogether. Essential oils and other natural compounds have emerged recently as alternative substances that can get rid of pathogenic bacteria, but researchers have had a hard time translating their antibacterial activity into treatments. Vincent M. Rotello and colleagues wanted to address this challenge.

The researchers packaged peppermint oil and cinnamaldehyde, the compound in cinnamon responsible for its flavor and aroma, into silica nanoparticles. The microcapsule treatment was effective against four different types of bacteria, including one antibiotic-resistant strain. It also promoted the growth of fibroblasts, a cell type that is important in wound healing.

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

Nanoparticle-Stabilized Capsules for the Treatment of Bacterial Biofilms by Bradley Duncan, Xiaoning Li, Ryan F. Landis, Sung Tae Kim, Akash Gupta, Li-Sheng Wang, Rajesh Ramanathan, Rui Tang, Jeffrey A. Boerth, and Vincent M. Rotello. ACS Nano, Article ASAP
DOI: 10.1021/acsnano.5b01696 Publication Date (Web): June 17, 2015

Copyright © 2015 American Chemical Society

This paper is behind a paywall.

Nanotechnology research protocols for Environment, Health and Safety Studies in US and a nanomedicine characterization laboratory in the European Union

I have two items relating to nanotechnology and the development of protocols. The first item concerns the launch of a new web portal by the US National Institute of Standards and Technology.

US National Institute of Standards and Technology (NIST)

From a July 1, 2015 news item on Azonano,

As engineered nanomaterials increasingly find their way into commercial products, researchers who study the potential environmental or health impacts of those materials face a growing challenge to accurately measure and characterize them. These challenges affect measurements of basic chemical and physical properties as well as toxicology assessments.

To help nano-EHS (Environment, Health and Safety)researchers navigate the often complex measurement issues, the National Institute of Standards and Technology (NIST) has launched a new website devoted to NIST-developed (or co-developed) and validated laboratory protocols for nano-EHS studies.

A July 1, 2015 NIST news release on EurekAlert, which originated the news item, offers more details about the information available through the web portal,

In common lab parlance, a “protocol” is a specific step-by-step procedure used to carry out a measurement or related activity, including all the chemicals and equipment required. Any peer-reviewed journal article reporting an experimental result has a “methods” section where the authors document their measurement protocol, but those descriptions are necessarily brief and condensed, and may lack validation of any sort. By comparison, on NIST’s new Protocols for Nano-EHS website the protocols are extraordinarily detailed. For ease of citation, they’re published individually–each with its own unique digital object identifier (DOI).

The protocols detail not only what you should do, but why and what could go wrong. The specificity is important, according to program director Debra Kaiser, because of the inherent difficulty of making reliable measurements of such small materials. “Often, if you do something seemingly trivial–use a different size pipette, for example–you get a different result. Our goal is to help people get data they can reproduce, data they can trust.”

A typical caution, for example, notes that if you’re using an instrument that measures the size of nanoparticles in a solution by how they scatter light, it’s important also to measure the transmission spectrum of the particles if they’re colored, because if they happen to absorb light strongly at the same frequency as your instrument, the result may be biased.

“These measurements are difficult because of the small size involved,” explains Kaiser. “Very few new instruments have been developed for this. People are adapting existing instruments and methods for the job, but often those instruments are being operated close to their limits and the methods were developed for chemicals or bulk materials and not for nanomaterials.”

“For example, NIST offers a reference material for measuring the size of gold nanoparticles in solution, and we report six different sizes depending on the instrument you use. We do it that way because different instruments sense different aspects of a nanoparticle’s dimensions. An electron microscope is telling you something different than a dynamic light scattering instrument, and the researcher needs to understand that.”

The nano-EHS protocols offered by the NIST site, Kaiser says, could form the basis for consensus-based, formal test methods such as those published by ASTM and ISO.

NIST’s nano-EHS protocol site currently lists 12 different protocols in three categories: sample preparation, physico-chemical measurements and toxicological measurements. More protocols will be added as they are validated and documented. Suggestions for additional protocols are welcome at nanoprotocols@nist.gov.

The next item concerns European nanomedicine.

CEA-LETI and Europe’s first nanomedicine characterization laboratory

A July 1, 2015 news item on Nanotechnology Now describes the partnership which has led to launch of the new laboratory,

CEA-Leti today announced the launch of the European Nano-Characterisation Laboratory (EU-NCL) funded by the European Union’s Horizon 2020 research and innovation programm[1]e. Its main objective is to reach a level of international excellence in nanomedicine characterisation for medical indications like cancer, diabetes, inflammatory diseases or infections, and make it accessible to all organisations developing candidate nanomedicines prior to their submission to regulatory agencies to get the approval for clinical trials and, later, marketing authorization.

“As reported in the ETPN White Paper[2], there is a lack of infrastructure to support nanotechnology-based innovation in healthcare,” said Patrick Boisseau, head of business development in nanomedicine at CEA-Leti and chairman of the European Technology Platform Nanomedicine (ETPN). “Nanocharacterisation is the first bottleneck encountered by companies developing nanotherapeutics. The EU-NCL project is of most importance for the nanomedicine community, as it will contribute to the competiveness of nanomedicine products and tools and facilitate regulation in Europe.”

EU-NCL is partnered with the sole international reference facility, the Nanotechnology Characterization Lab of the National Cancer Institute in the U.S. (US-NCL)[3], to get faster international harmonization of analytical protocols.

“We are excited to be part of this cooperative arrangement between Europe and the U.S.,” said Scott E. McNeil, director of U.S. NCL. “We hope this collaboration will help standardize regulatory requirements for clinical evaluation and marketing of nanomedicines internationally. This venture holds great promise for using nanotechnologies to overcome cancer and other major diseases around the world.”

A July 2, 2015 EMPA (Swiss Federal Laboratories for Materials Science and Technology) news release on EurekAlert provides more detail about the laboratory and the partnerships,

The «European Nanomedicine Characterization Laboratory» (EU-NCL), which was launched on 1 June 2015, has a clear-cut goal: to help bring more nanomedicine candidates into the clinic and on the market, for the benefit of patients and the European pharmaceutical industry. To achieve this, EU-NCL is partnered with the sole international reference facility, the «Nanotechnology Characterization Laboratory» (US-NCL) of the US-National Cancer Institute, to get faster international harmonization of analytical protocols. EU-NCL is also closely connected to national medicine agencies and the European Medicines Agency to continuously adapt its analytical services to requests of regulators. EU-NCL is designed, organized and operated according to the highest EU regulatory and quality standards. «We are excited to be part of this cooperative project between Europe and the U.S.,» says Scott E. McNeil, director of US-NCL. «We hope this collaboration will help standardize regulatory requirements for clinical evaluation and marketing of nanomedicines internationally. This venture holds great promise for using nanotechnologies to overcome cancer and other major diseases around the world.»

Nine partners from eight countries

EU-NCL, which is funded by the EU for a four-year period with nearly 5 million Euros, brings together nine partners from eight countries: CEA-Tech in Leti and Liten, France, the coordinator of the project; the Joint Research Centre of the European Commission in Ispra, Italy; European Research Services GmbH in Münster Germany; Leidos Biomedical Research, Inc. in Frederick, USA; Trinity College in Dublin, Ireland; SINTEF in Oslo, Norway; the University of Liverpool in the UK; Empa, the Swiss Federal Laboratories for Materials Science and Technology in St. Gallen, Switzerland; Westfälische Wilhelms-Universität (WWU) and Gesellschaft für Bioanalytik, both in Münster, Germany. Together, the partnering institutions will provide a trans-disciplinary testing infrastructure covering a comprehensive set of preclinical characterization assays (physical, chemical, in vitro and in vivo biological testing), which will allow researchers to fully comprehend the biodistribution, metabolism, pharmacokinetics, safety profiles and immunological effects of their medicinal nano-products. The project will also foster the use and deployment of standard operating procedures (SOPs), benchmark materials and quality management for the preclinical characterization of medicinal nano-products. Yet another objective is to promote intersectoral and interdisciplinary communication among key drivers of innovation, especially between developers and regulatory agencies.

The goal: to bring safe and efficient nano-therapeutics faster to the patient

Within EU-NCL, six analytical facilities will offer transnational access to their existing analytical services for public and private developers, and will also develop new or improved analytical assays to keep EU-NCL at the cutting edge of nanomedicine characterization. A complementary set of networking activities will enable EU-NCL to deliver to European academic or industrial scientists the high-quality analytical services they require for accelerating the industrial development of their candidate nanomedicines. The Empa team of Peter Wick at the «Particles-Biology Interactions» lab will be in charge of the quality management of all analytical methods, a key task to guarantee the best possible reproducibility and comparability of the data between the various analytical labs within the consortium. «EU-NCL supports our research activities in developing innovative and safe nanomaterials for healthcare within an international network, which will actively shape future standards in nanomedicine and strengthen Empa as an enabler to facilitate the transfer of novel nanomedicines from bench to bedside», says Wick.

You can find more information about the laboratory on the Horizon 2020 (a European Union science funding programme) project page for the EU-NCL laboratory. For anyone curious about CEA-Leti, it’s a double-layered organization. CEA is France’s Commission on Atomic Energy and Alternative Energy (Commissariat à l’énergie atomique et aux énergies alternatives); you can go here to their French language site (there is an English language clickable option on the page). Leti is one of the CEA’s institutes and is known as either Leti or CEA-Leti. I have no idea what Leti stands for. Here’s the Leti website (this is the English language version).

Informal roundup of robot movies and television programmes and a glimpse into our robot future

David Bruggeman has written an informal series of posts about robot movies. The latest, a June 27, 2015 posting on his Pasco Phronesis blog, highlights the latest Terminator film and opines that the recent interest could be traced back to the rebooted Battlestar Galactica television series (Note: Links have been removed),

I suppose this could be traced back to the reboot of Battlestar Galactica over a decade ago, but robots and androids have become an increasing presence on film and television, particularly in the last 2 years.

In the movies, the new Terminator film comes out next week, and the previews suggest we will see a new generation of killer robots traveling through time and space.  Chappie is now out on your digital medium of choice (and I’ll post about any science fiction science policy/SciFiSciPol once I see it), so you can compare its robot police to those from either edition of Robocop or the 2013 series Almost Human.  Robots also have a role …

The new television series he mentions, Humans (click on About) debuted on the US tv channel, AMC, on Sunday, June 28, 2015 (yesterday).

HUMANS is set in a parallel present, where the latest must-have gadget for any busy family is a Synth – a highly-developed robotic servant, eerily similar to its live counterpart. In the hope of transforming the way his family lives, father Joe Hawkins (Tom Goodman-Hill) purchases a Synth (Gemma Chan) against the wishes of his wife (Katharine Parkinson), only to discover that sharing life with a machine has far-reaching and chilling consequences.

Here’s a bit more information from its Wikipedia entry,

Humans (styled as HUM∀NS) is a British-American science fiction television series, debuted in June 2015 on Channel 4 and AMC.[2] Written by the British team Sam Vincent and Jonathan Brackley, based on the award-winning Swedish science fiction drama Real Humans, the series explores the emotional impact of the blurring of the lines between humans and machines. The series is produced jointly by AMC, Channel 4 and Kudos.[3] The series will consist of eight episodes.[4]

David also wrote about Ex Machina, a recent robot film with artistic ambitions, in an April 26, 2015 posting on his Pasco Phronesis blog,

I finally saw Ex Machina, which recently opened in the United States.  It’s a minimalist film, with few speaking roles and a plot revolving around an intelligence test.  Of the robot movies out this year, it has received the strongest reviews, and it may take home some trophies during the next awards season.  Shot in Norway, the film is both lovely to watch and tricky to engage.  I finished the film not quite sure what the characters were thinking, and perhaps that’s a lesson from the film.

Unlike Chappie and Automata, the intelligent robot at the center of Ex Machina is not out in the world. …

He started the series with a Feb. 8, 2015 posting which previews the movies in his later postings but also includes a couple of others not mentioned in either the April or June posting, Avengers: Age of Ultron and Spare Parts.

It’s interesting to me that these robots  are mostly not related to the benign robots in the movie, ‘Forbidden Planet’, a reworking of Shakespeare’s The Tempest in outer space, in ‘Lost in Space’, a 1960s television programme, and in the Jetsons animated tv series of the 1960s. As far as I can tell not having seen the new movies in question, the only benign robot in the current crop would be ‘Chappie’. It should be mentioned that the ‘Terminator’, in the person of Arnold Schwarzenegger, has over a course of three or four movies evolved from a destructive robot bent on evil to a destructive robot working on behalf of good.

I’ll add one more more television programme and I’m not sure if the robot boy is good or evil but there’s Extant where Halle Berry’s robot son seems to be in a version of the Pinocchio story (an ersatz child want to become human), which is enjoying its second season on US television as of July 1, 2015.

Regardless of one or two ‘sweet’ robots, there seems to be a trend toward ominous robots and perhaps, in addition to Battlestar Galactica, the concerns being raised by prominent scientists such as Stephen Hawking and those associated with the Centre for Existential Risk at the University of Cambridge have something to do with this trend and may partially explain why Chappie did not do as well at the box office as hoped. Thematically, it was swimming against the current.

As for a glimpse into the future, there’s this Children’s Hospital of Los Angeles June 29, 2015 news release,

Many hospitals lack the resources and patient volume to employ a round-the-clock, neonatal intensive care specialist to treat their youngest and sickest patients. Telemedicine–with real-time audio and video communication between a neonatal intensive care specialist and a patient–can provide access to this level of care.

A team of neonatologists at Children’s Hospital Los Angeles investigated the use of robot-assisted telemedicine in performing bedside rounds and directing daily care for infants with mild-to-moderate disease. They found no significant differences in patient outcomes when telemedicine was used and noted a high level of parent satisfaction. This is the first published report of using telemedicine for patient rounds in a neonatal intensive care unit (NICU). Results will be published online first on June 29 in the Journal of Telemedicine and Telecare.

Glimpse into the future?

The part I find most fascinating was that there was no difference in outcomes, moreover, the parents’ satisfaction rate was high when robots (telemedicine) were used. Finally, of the families who completed the after care survey (45%), all indicated they would be comfortable with another telemedicine (robot) experience. My comment, should robots prove to be cheaper in the long run and the research results hold as more studies are done, I imagine that hospitals will introduce them as a means of cost cutting.

Mexican company “Medical and Surgical Center for Retina” and its painless eye drop treatment

I am confined to the materials which have been translated into English so this story is lighter on detail than I would prefer. A June 26, 2015 news item on Azonano describes a company which provides a new painless treatment for secondary blindness,

The Mexican company “Medical and Surgical Center for Retina” created a way to transport drugs, in order to avoid risks and painful treatments in people with secondary blindness due to chronic degenerative blindness such as diabetic retinopathy and degeneration of the eye. The innovative formula results eliminates the need to administrate the drug by intraocular injection.

It is a nanotechnology product, which works with last generation liposomes particles, concentrated in droplets, which function as a conveyor that wraps proteins or antibody fragments and allow its passage into the eye. Once inside, it releases the drugs.

With the nanotechnology product the costs are reduced by 80 to 90 percent and enables the elderly population to make use of it. “With this technology hospitals that have no resources can apply the needed drugs, without requiring a a specialist or a particular facility for the administration. It is necessary to be prescribed by a physician, but it can be administered at home, which lowers the cost. “

A June 25, 2015 Investigación y Desarrollo news release on Alpha Galileo, which originated the news item, provides more information about the company and what seems to be a series of clinical trials both current and upcoming,

The doctor Juan Carlos Altamirano Vallejo, medical director of the Medical and Surgical Center for Retina, mentions that the conditions that originate in the retina are mostly caused by chronic degenerative diseases such as diabetes (diabetic retinopathy) or macular alteration . Patients with this conditions usually require one injection per month which comes at a very high cost and increases if the procedure is needed for both eyes.

The company, located in Jalisco (central west state of Mexico) won the Mexican National Prize for Technology and Innovation and plans to conclude the Clinical Research regulated by the Federal Commission for Protection Against Health Risks (COFEPRIS) next year. The idea is for the medicine to be distributed in state and private health institutions. So far, the achieved results are the same as the ones obtained with intraocular injection, but without the inherent risks of this procedure, such as infection or retinal detachment.

Current talks are being held with COFEPRIS to conduct a study within several diseases and increase its use for different conditions. In the United States, patients who have followed the treatment have had positive results.

The Medical and Surgical Center for Retina provides medical care and a specialized retina Ophthalmology Clinic provides consultation, which also has an area of ​​Biotechnology and Drug Research of Biomedical Engineering, Diagnosis and Treatment Equipment.

Altamirano Vallejo says that receiving the award opens the doors to reach more people and prevent blindness. “It is the most important prize delivered by the Presidency of the Republic in the area of ​​technology and innovation. For us, to have an entity such as the award foundation to guide us and allows us to learn, know skills, strengths and company administration makes us proud, specially the opportunity for a product like this to reach the market and prevent blindness.

Back in an Oct. 9, 2014 posting, I wrote about a couple of nanotechnology-enabled eye drop projects and some of the challenges with trying to bypass the eye’s natural protections.

Finally, I was not able to locate the company (without the Spanish language name that’s not likely to be easy) but there is more information about Investigación y Desarrollo here.

Crowdfund nano spies for cancer

University of Groningen (Netherlands) researcher, Romana Schirhagl, is crowdfunding her development of a new technique (using nanodiamonds) for biomedical research which would allow observation of free radicals in cells. From a June 25, 2015 news item on Nanowerk,

Romana Schirhagl, a researcher at the University Medical Center Groningen, is hoping to garner public support for a new form of cancer research. Schirhagl wants to introduce miniscule diamonds into living cancer cells. Like spies, these nanodiamonds will be on a mission to reveal the secrets of the cell. Schirhagl applies a unique combination of knowledge and techniques from physics, chemistry and medicine in the research. This could form the basis of new and improved cancer drugs.

A June 16, 2015 University of Groningen press release, which originated the news item, provides background information for the research,

The research of Schirhagl and her research group in the department of Biomedical Engineering focuses on the behaviour of free radicals in a cell. These radicals have an important role in the body. They are sometimes extremely useful, as in the immune system, where they help fight bacteria and viruses, but sometimes very harmful, as when they actually harm healthy cells and can cause cancer. As the radicals only exist for a fraction of a second, it is difficult to tell them apart and study them.

New technique

Schirhagl wants to apply a new technique that currently is mainly used in fundamental physics but looks extremely promising for biomedical research. The technique is based on very small diamonds that can ‘sense’ the presence of magnetic fields from the radicals. The nanodiamonds are fluorescent and change in luminosity as a response to their environment. This makes it easier to determine which radicals occur when and how they work. This information should make it possible to improve cancer drugs – which themselves sometimes use free radicals – or even develop new ones.

Unexpectedly, the crowdfunding platform is the University of Groningen’s own. You can find out more about Nano spies here. To date the project has raised over 6,600 Euros towards a goal of 20,000 Euros.

A pragmatic approach to alternatives to animal testing

Retitled and cross-posted from the June 30, 2015 posting (Testing times: the future of animal alternatives) on the International Innovation blog (a CORDIS-listed project dissemination partner for FP7 and H2020 projects).

Maryse de la Giroday explains how emerging innovations can provide much-needed alternatives to animal testing. She also shares highlights of the 9th World Congress on Alternatives to Animal Testing.

‘Guinea pigging’ is the practice of testing drugs that have passed in vitro and in vivo tests on healthy humans in a Phase I clinical trial. In fact, healthy humans can make quite a bit of money as guinea pigs. The practice is sufficiently well-entrenched that there is a magazine, Guinea Pig Zero, devoted to professionals. While most participants anticipate some unpleasant side effects, guinea pigging can sometimes be a dangerous ‘profession’.

HARMFUL TO HEALTH

One infamous incident highlighting the dangers of guinea pigging occurred in 2006 at Northwick Park Hospital outside London. Volunteers were offered £2,000 to participate in a Phase I clinical trial to test a prospective treatment – a monoclonal antibody designed for rheumatoid arthritis and multiple sclerosis. The drug, called TGN1412, caused catastrophic systemic organ failure in participants. All six individuals receiving the drug required hospital treatment. One participant reportedly underwent amputation of fingers and toes. Another reacted with symptoms comparable to John Merrick, the Elephant Man.

The root of the disaster lay in subtle immune system differences between humans and cynomolgus monkeys – the model animal tested prior to the clinical trial. The drug was designed for the CD28 receptor on T cells. The monkeys’ receptors closely resemble those found in humans. However, unlike these monkeys, humans have other immune cells that carry CD28. The trial participants received a starting dosage that was 0.2 per cent of what the monkeys received in their final tests, but failure to take these additional receptors into account meant a dosage that was supposed to occupy 10 per cent of the available CD28 receptors instead occupied 90 per cent. After the event, a Russian inventor purchased the commercial rights to the drug and renamed it TAB08. It has been further developed by Russian company, TheraMAB, and TAB08 is reportedly in Phase II clinical trials.

HUMAN-ON-A-CHIP AND ORGANOID PROJECTS

While animal testing has been a powerful and useful tool for determining safe usage for pharmaceuticals and other types of chemicals, it is also a cruel and imperfect practice. Moreover, it typically only predicts 30-60 per cent of human responses to new drugs. Nanotechnology and other emerging innovations present possibilities for reducing, and in some cases eliminating, the use of animal models.

People for the Ethical Treatment of Animals (PETA), still better known for its publicity stunts, maintains a webpage outlining a number of alternatives including in silico testing (computer modelling), and, perhaps most interestingly, human-on-a-chip and organoid (tissue engineering) projects.

Organ-on-a-chip projects use stem cells to create human tissues that replicate the functions of human organs. Discussions about human-on-a-chip activities – a phrase used to describe 10 interlinked organ chips – were a highlight of the 9th World Congress on Alternatives to Animal Testing held in Prague, Czech Republic, last year. One project highlighted at the event was a joint US National Institutes of Health (NIH), US Food and Drug Administration (FDA) and US Defense Advanced Research Projects Agency (DARPA) project led by Dan Tagle that claimed it would develop functioning human-on-a-chip by 2017. However, he and his team were surprisingly close-mouthed and provided few details making it difficult to assess how close they are to achieving their goal.

By contrast, Uwe Marx – Leader of the ‘Multi-Organ-Chip’ programme in the Institute of Biotechnology at the Technical University of Berlin and Scientific Founder of TissUse, a human-on-a-chip start-up company – claims to have sold two-organ chips. He also claims to have successfully developed a four-organ chip and that he is on his way to building a human-on-a-chip. Though these chips remain to be seen, if they are, they will integrate microfluidics, cultured cells and materials patterned at the nanoscale to mimic various organs, and will allow chemical testing in an environment that somewhat mirrors a human.

Another interesting alternative for animal testing is organoids – a feature in regenerative medicine that can function as test sites. Engineers based at Cornell University recently published a paper on their functional, synthetic immune organ. Inspired by the lymph node, the organoid is comprised of gelatin-based biomaterials, which are reinforced with silicate nanoparticles (to keep the tissue from melting when reaching body temperature) and seeded with cells allowing it to mimic the anatomical microenvironment of a lymphatic node. It behaves like its inspiration converting B cells to germinal centres which activate, mature and mutate antibody genes when the body is under attack. The engineers claim to be able to control the immune response and to outperform 2D cultures with their 3D organoid. If the results are reproducible, the organoid could be used to develop new therapeutics.

Maryse de la Giroday is a science communications consultant and writer.

Full disclosure: Maryse de la Giroday received transportation and accommodation for the 9th World Congress on Alternatives to Animal Testing from SEURAT-1, a European Union project, making scientific inquiries to facilitate the transition to animal testing alternatives, where possible.

ETA July 1, 2015: I would like to acknowledge more sources for the information in this article,

Sources:

The guinea pigging term, the ‘professional aspect, the Northwick Park story, and the Guinea Pig Zero magazine can be found in Carl Elliot’s excellent 2006 story titled ‘Guinea-Pigging’ for New Yorker magazine.

http://www.newyorker.com/magazine/2008/01/07/guinea-pigging

Information about the drug used in the Northwick Park Hospital disaster, the sale of the rights to a Russian inventor, and the June 2015 date for the current Phase II clinical trials were found in this Wikipedia essay titled, TGN 1412.

http://en.wikipedia.org/wiki/TGN1412

Additional information about the renamed drug, TAB08 and its Phase II clinical trials was found on (a) a US government website for information on clinical trials, (b) in a Dec. 2014 (?) TheraMAB  advertisement in a Nature group magazine and a Jan. 2014 press release,

https://www.clinicaltrials.gov/ct2/show/NCT01990157?term=TAB08_RA01&rank=1

http://www.theramab.ru/TheraMAB_NAture.pdf

http://theramab.ru/en/news/phase_II

An April 2015 article (Experimental drug that injured UK volunteers resumes in human trials) by Owen Dyer for the British Medical Journal also mentioned the 2015 TheraMab Phase II clinical trials and provided information about the information about Macaque (cynomolgus) monkey tests.

http://www.bmj.com.proxy.lib.sfu.ca/content/350/bmj.h1831

BMJ 2015; 350 doi: http://dx.doi.org.proxy.lib.sfu.ca/10.1136/bmj.h1831 (Published 02 April 2015) Cite this as: BMJ 2015;350:h1831

A 2009 study by Christopher Horvath and Mark Milton somewhat contradicts the Dyer article’s contention that a species Macaque monkey was used as an animal model. (As the Dyer article is more recent and the Horvath/Milton analysis is more complex covering TGN 1412 in the context of other MAB drugs and their precursor tests along with specific TGN 1412 tests, I opted for the simple description.)

The TeGenero Incident [another name for the Northwick Park Accident] and the Duff Report Conclusions: A Series of Unfortunate Events or an Avoidable Event? by Christopher J. Horvath and Mark N. Milton. Published online before print February 24, 2009, doi: 10.1177/0192623309332986 Toxicol Pathol April 2009 vol. 37 no. 3 372-383

http://tpx.sagepub.com/content/37/3/372.full

Philippa Roxbuy’s May 24, 2013 BBC news online article provided confirmation and an additional detail or two about the Northwick Park Hospital accident. It notes that other models, in addition to animal models, are being developed.

http://www.bbc.com/news/health-22556736

Anne Ju’s excellent June 10,2015 news release about the Cornell University organoid (synthetic immune organ) project was very helpful.

http://www.news.cornell.edu/stories/2015/06/engineers-synthetic-immune-organ-produces-antibodies

There will also be a magazine article in International Innovation, which will differ somewhat from the blog posting, due to editorial style and other requirements.

ETA July 22, 2015: I now have a link to the magazine article.

Clinical trial for bionic eye (artificial retinal implant) shows encouraging results (safety and efficacy)

The Argus II artificial retina was first mentioned here in a Feb. 15, 2013 posting (scroll down about 50% of the way) when it received US Food and Drug Administration (FDA) commercial approval. In retrospect that seems puzzling since the results of a three-year clinical trial have just been reported in a June 23, 2015 news item on ScienceDaily (Note: There was one piece of information about the approval which didn’t make its way into the information disseminated in 2013),

The three-year clinical trial results of the retinal implant popularly known as the “bionic eye,” have proven the long-term efficacy, safety and reliability of the device that restores vision in those blinded by a rare, degenerative eye disease. The findings show that the Argus II significantly improves visual function and quality of life for people blinded by retinitis pigmentosa. They are being published online in Ophthalmology, the journal of the American Academy of Ophthalmology.

A June 23, 2015 American Academy of Ophthalmology news release (also on EurekAlert), which originated the news item, describes the condition the Argus II is designed for and that crucial bit of FDA information,

Retinitis pigmentosa is an incurable disease that affects about 1 in 4,000 Americans and causes slow vision loss that eventually leads to blindness.[1] The Argus II system was designed to help provide patients who have lost their sight due to the disease with some useful vision. Through the device, patients with retinitis pigmentosa are able to see patterns of light that the brain learns to interpret as an image. The system uses a miniature video camera stored in the patient’s glasses to send visual information to a small computerized video processing unit which can be stored in a pocket. This computer turns the image to electronic signals that are sent wirelessly to an electronic device implanted on the retina, the layer of light-sensing cells lining the back of the eye.

The Argus II received Food and Drug Administration (FDA) approval as a Humanitarian Use Device (HUD) in 2013, which is an approval specifically for devices intended to benefit small populations and/or rare conditions. [emphasis mine]

I don’t recall seeing “Humanitarian Use Device (HUD)” in the 2013 materials which focused on the FDA’s commercial use approval. I gather from this experience that commercial use doesn’t necessarily mean they’ve finished with clinical trials and are ready to start selling the product. In any event, I will try to take a closer look at the actual approvals the next time, assuming I can make sense of the language.

After all the talk about it, here’s what the device looks like,

 Caption: Figure A, The implanted portions of the Argus II System. Figure B, The external components of the Argus II System. Images in real time are captured by camera mounted on the glasses. The video processing unit down-samples and processes the image, converting it to stimulation patterns. Data and power are sent via radiofrequency link form the transmitter antenna on the glasses to the receiver antenna around the eye. A removable, rechargeable battery powers the system. Credit: Photo courtesy of Second Sight Medical Products, Inc.


Caption: Figure A, The implanted portions of the Argus II System. Figure B, The external components of the Argus II System. Images in real time are captured by camera mounted on the glasses. The video processing unit down-samples and processes the image, converting it to stimulation patterns. Data and power are sent via radiofrequency link form the transmitter antenna on the glasses to the receiver antenna around the eye. A removable, rechargeable battery powers the system.
Credit: Photo courtesy of Second Sight Medical Products, Inc.

The news release offers more details about the recently completed clinical trial,

To further evaluate the safety, reliability and benefit of the device, a clinical trial of 30 people, aged 28 to 77, was conducted in the United States and Europe. All of the study participants had little or no light perception in both eyes. The researchers conducted visual function tests using both a computer screen and real-world conditions, including finding and touching a door and identifying and following a line on the ground. A Functional Low-vision Observer Rated Assessment (FLORA) was also performed by independent visual rehabilitation experts at the request of the FDA to assess the impact of the Argus II system on the subjects’ everyday lives, including extensive interviews and tasks performed around the home.

The visual function results indicated that up to 89 percent of the subjects performed significantly better with the device. The FLORA found that among the subjects, 80 percent received benefit from the system when considering both functional vision and patient-reported quality of life, and no subjects were affected negatively.

After one year, two-thirds of the subjects had not experienced device- or surgery-related serious adverse events. After three years, there were no device failures. Throughout the three years, 11 subjects experienced serious adverse events, most of which occurred soon after implantation and were successfully treated. One of these treatments, however, was to remove the device due to recurring erosion after the suture tab on the device became damaged.

“This study shows that the Argus II system is a viable treatment option for people profoundly blind due to retinitis pigmentosa – one that can make a meaningful difference in their lives and provides a benefit that can last over time,” said Allen C. Ho, M.D., lead author of the study and director of the clinical retina research unit at Wills Eye Hospital. “I look forward to future studies with this technology which may make possible expansion of the intended use of the device, including treatment for other diseases and eye injuries.”

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

Long-Term Results from an Epiretinal Prosthesis to Restore Sight to the Blind by Allen C. Ho,Mark S. Humayun, Jessy D. Dorn, Lyndon da Cruz, Gislin Dagnelie,James Handa, Pierre-Olivier Barale, José-Alain Sahel, Paulo E. Stanga, Farhad Hafezi, Avinoam B. Safran, Joel Salzmann, Arturo Santos, David Birch, Rand Spencer, Artur V. Cideciyan, Eugene de Juan, Jacque L. Duncan, Dean Eliott, Amani Fawzi, Lisa C. Olmos de Koo, Gary C. Brown, Julia A. Haller, Carl D. Regillo, Lucian V. Del Priore, Aries Arditi, Duane R. Geruschat, Robert J. Greenberg. Opthamology, June 2015 http://dx.doi.org/10.1016/j.ophtha.2015.04.032

This paper is open access.