Tag Archives: neuroprosthetics

Xenotransplantation—organs for transplantation in human patients—it’s a business and a science

The last time (June 18, 2018 post) I mentioned xenotransplantation (transplanting organs from one species into another species; see more here), it was in the context of an art/sci (or sciart) event coming to Vancouver (Canada).,

Patricia Piccinini’s Curious Imaginings Courtesy: Vancouver Biennale [downloaded from http://dailyhive.com/vancouver/vancouver-biennale-unsual-public-art-2018/]

The latest edition of the Vancouver Biennale was featured in a June 6, 2018 news item on the Daily Hive (Vancouver),

Melbourne artist Patricia Piccinini’s Curious Imaginings is expected to be one of the most talked about installations of the exhibit. Her style of “oddly captivating, somewhat grotesque, human-animal hybrid creature” is meant to be shocking and thought-provoking.

Piccinini’s interactive [emphasis mine] experience will “challenge us to explore the social impacts of emerging biotechnology and our ethical limits in an age where genetic engineering and digital technologies are already pushing the boundaries of humanity.”

Piccinini’s work will be displayed in the 105-year-old Patricia Hotel in Vancouver’s Strathcona neighbourhood. The 90-day ticketed exhibition [emphasis mine] is scheduled to open this September [2018].

(The show opens on Sept. 14, 2018.)

At the time, I had yet to stumble across Ingfei Chen’s thoughtful dive into the topic in her May 9, 2018 article for Slate.com,

In the United States, the clock is ticking for more than 114,700 adults and children waiting for a donated kidney or other lifesaving organ, and each day, nearly 20 of them die. Researchers are devising a new way to grow human organs inside other animals, but the method raises potentially thorny ethical issues. Other conceivable futuristic techniques sound like dystopian science fiction. As we envision an era of regenerative medicine decades from now, how far is society willing to go to solve the organ shortage crisis?

I found myself pondering this question after a discussion about the promises of stem cell technologies veered from the intriguing into the bizarre. I was interviewing bioengineer Zev Gartner, co-director and research coordinator of the Center for Cellular Construction at the University of California, San Francisco, about so-called organoids, tiny clumps of organlike tissue that can self-assemble from human stem cells in a Petri dish. These tissue bits are lending new insights into how our organs form and diseases take root. Some researchers even hope they can nurture organoids into full-size human kidneys, pancreases, and other organs for transplantation.

Certain organoid experiments have recently set off alarm bells, but when I asked Gartner about it, his radar for moral concerns was focused elsewhere. For him, the “really, really thought-provoking” scenarios involve other emerging stem cell–based techniques for engineering replacement organs for people, he told me. “Like blastocyst complementation,” he said.

Never heard of it? Neither had I. Turns out it’s a powerful new genetic engineering trick that researchers hope to use for growing human organs inside pigs or sheep—organs that could be genetically personalized for transplant patients, in theory avoiding immune-system rejection problems. The science still has many years to go, but if it pans out, it could be one solution to the organ shortage crisis. However, the prospect of creating hybrid animals with human parts and killing them to harvest organs has already raised a slew of ethical questions. In 2015, the National Institutes of Health placed a moratorium on federal funding of this nascent research area while it evaluated and discussed the issues.

As Gartner sees it, the debate over blastocyst complementation research—work that he finds promising—is just one of many conversations that society needs to have about the ethical and social costs and benefits of future technologies for making lifesaving transplant organs. “There’s all these weird ways that we could go about doing this,” he said, with a spectrum of imaginable approaches that includes organoids, interspecies organ farming, and building organs from scratch using 3D bioprinters. But even if it turns out we can produce human organs in these novel ways, the bigger issue, in each technological instance, may be whether we should.

Gartner crystallized things with a downright creepy example: “We know that the best bioreactor for tissues and organs for humans are human beings,” he said. Hypothetically, “the best way to get you a new heart would be to clone you, grow up a copy of yourself, and take the heart out.” [emphasis mine] Scientists could probably produce a cloned person with the technologies we already have, if money and ethics were of no concern. “But we don’t want to go there, right?” he added in the next breath. “The ethics involved in doing it are not compatible with who we want to be as a society.”

This sounds like Gartner may have been reading some science fiction, specifically, Lois McMaster Bujold and her Barrayar series where she often explored the ethics and possibilities of bioengineering. At this point, some of her work seems eerily prescient.

As for Chen’s article, I strongly encourage you to read it in its entirety if you have the time.

Medicine, healing, and big money

At about the same time, there was a May 31, 2018 news item on phys.org offering a perspective from some of the leaders in the science and the business (Note: Links have been removed),

Over the past few years, researchers led by George Church have made important strides toward engineering the genomes of pigs to make their cells compatible with the human body. So many think that it’s possible that, with the help of CRISPR technology, a healthy heart for a patient in desperate need might one day come from a pig.

“It’s relatively feasible to change one gene in a pig, but to change many dozens—which is quite clear is the minimum here—benefits from CRISPR,” an acronym for clustered regularly interspaced short palindromic repeats, said Church, the Robert Winthrop Professor of Genetics at Harvard Medical School (HMS) and a core faculty member of Harvard’s Wyss Institute for Biologically Inspired Engineering. Xenotransplantation is “one of few” big challenges (along with gene drives and de-extinction, he said) “that really requires the ‘oomph’ of CRISPR.”

To facilitate the development of safe and effective cells, tissues, and organs for future medical transplantation into human patients, Harvard’s Office of Technology Development has granted a technology license to the Cambridge biotech startup eGenesis.

Co-founded by Church and former HMS doctoral student Luhan Yang in 2015, eGenesis announced last year that it had raised $38 million to advance its research and development work. At least eight former members of the Church lab—interns, doctoral students, postdocs, and visiting researchers—have continued their scientific careers as employees there.

“The Church Lab is well known for its relentless pursuit of scientific achievements so ambitious they seem improbable—and, indeed, [for] its track record of success,” said Isaac Kohlberg, Harvard’s chief technology development officer and senior associate provost. “George deserves recognition too for his ability to inspire passion and cultivate a strong entrepreneurial drive among his talented research team.”

The license from Harvard OTD covers a powerful set of genome-engineering technologies developed at HMS and the Wyss Institute, including access to foundational intellectual property relating to the Church Lab’s 2012 breakthrough use of CRISPR, led by Yang and Prashant Mali, to edit the genome of human cells. Subsequent innovations that enabled efficient and accurate editing of numerous genes simultaneously are also included. The license is exclusive to eGenesis but limited to the field of xenotransplantation.

A May 30, 2018 Harvard University news release by Caroline Petty, which originated the news item, explores some of the issues associated with incubating humans organs in other species,

The prospect of using living, nonhuman organs, and concerns over the infectiousness of pathogens either present in the tissues or possibly formed in combination with human genetic material, have prompted the Food and Drug Administration to issue detailed guidance on xenotransplantation research and development since the mid-1990s. In pigs, a primary concern has been that porcine endogenous retroviruses (PERVs), strands of potentially pathogenic DNA in the animals’ genomes, might infect human patients and eventually cause disease. [emphases mine]

That’s where the Church lab’s CRISPR expertise has enabled significant advances. In 2015, the lab published important results in the journal Science, successfully demonstrating the use of genome engineering to eliminate all 62 PERVs in porcine cells. Science later called it “the most widespread CRISPR editing feat to date.”

In 2017, with collaborators at Harvard, other universities, and eGenesis, Church and Yang went further. Publishing again in Science, they first confirmed earlier researchers’ fears: Porcine cells can, in fact, transmit PERVs into human cells, and those human cells can pass them on to other, unexposed human cells. (It is still unknown under what circumstances those PERVs might cause disease.) In the same paper, they corrected the problem, announcing the embryogenesis and birth of 37 PERV-free pigs. [Note: My July 17, 2018 post features research which suggests CRISPR-Cas9 gene editing may cause greater genetic damage than had been thought.]

“Taken together, those innovations were stunning,” said Vivian Berlin, director of business development in OTD, who manages the commercialization strategy for much of Harvard’s intellectual property in the life sciences. “That was the foundation they needed, to convince both the scientific community and the investment community that xenotransplantation might become a reality.”

“After hundreds of tests, this was a critical milestone for eGenesis — and the entire field — and represented a key step toward safe organ transplantation from pigs,” said Julie Sunderland, interim CEO of eGenesis. “Building on this study, we hope to continue to advance the science and potential of making xenotransplantation a safe and routine medical procedure.”

Genetic engineering may undercut human diseases, but also could help restore extinct species, researcher says. [Shades of the Jurassic Park movies!]

It’s not, however, the end of the story: An immunological challenge remains, which eGenesis will need to address. The potential for a patient’s body to outright reject transplanted tissue has stymied many previous attempts at xenotransplantation. Church said numerous genetic changes must be achieved to make porcine organs fully compatible with human patients. Among these are edits to several immune functions, coagulation functions, complements, and sugars, as well as the PERVs.

“Trying the straight transplant failed almost immediately, within hours, because there’s a huge mismatch in the carbohydrates on the surface of the cells, in particular alpha-1-3-galactose, and so that was a showstopper,” Church explained. “When you delete that gene, which you can do with conventional methods, you still get pretty fast rejection, because there are a lot of other aspects that are incompatible. You have to take care of each of them, and not all of them are just about removing things — some of them you have to humanize. There’s a great deal of subtlety involved so that you get normal pig embryogenesis but not rejection.

“Putting it all together into one package is challenging,” he concluded.

In short, it’s the next big challenge for CRISPR.

Not unexpectedly, there is no mention of the CRISPR patent fight between Harvard/MIT’s (Massachusetts Institute of Technology) Broad Institute and the University of California at Berkeley (UC Berkeley). My March 15, 2017 posting featured an outcome where the Broad Institute won the first round of the fight. As I recall, it was a decision based on the principles associated with King Solomon, i.e., the US Patent Office, divided the baby and UCBerkeley got the less important part of the baby. As you might expect the decision has been appealed. In an April 30, 2018 piece, Scientific American reprinted an article about the latest round in the fight written by Sharon Begley for STAT (Note: Links have been removed),

All You Need to Know for Round 2 of the CRISPR Patent Fight

It’s baaaaack, that reputation-shredding, stock-moving fight to the death over key CRISPR patents. On Monday morning in Washington, D.C., the U.S. Court of Appeals for the Federal Circuit will hear oral arguments in University of California v. Broad Institute. Questions?

How did we get here? The patent office ruled in February 2017 that the Broad’s 2014 CRISPR patent on using CRISPR-Cas9 to edit genomes, based on discoveries by Feng Zhang, did not “interfere” with a patent application by UC based on the work of UC Berkeley’s Jennifer Doudna. In plain English, that meant the Broad’s patent, on using CRISPR-Cas9 to edit genomes in eukaryotic cells (all animals and plants, but not bacteria), was different from UC’s, which described Doudna’s experiments using CRISPR-Cas9 to edit DNA in a test tube—and it was therefore valid. The Patent Trial and Appeal Board concluded that when Zhang got CRISPR-Cas9 to work in human and mouse cells in 2012, it was not an obvious extension of Doudna’s earlier research, and that he had no “reasonable expectation of success.” UC appealed, and here we are.

For anyone who may not realize what the stakes are for these institutions, Linda Williams in a March 16, 1999 article for the LA Times had this to say about universities, patents, and money,

The University of Florida made about $2 million last year in royalties on a patent for Gatorade Thirst Quencher, a sports drink that generates some $500 million to $600 million a year in revenue for Quaker Oats Co.

The payments place the university among the top five in the nation in income from patent royalties.

Oh, but if some people on the Gainesville, Fla., campus could just turn back the clock. “If we had done Gatorade right, we would be getting $5 or $6 million (a year),” laments Donald Price, director of the university’s office of corporate programs. “It is a classic example of how not to handle a patent idea,” he added.

Gatorade was developed in 1965 when many universities were ill equipped to judge the commercial potential of ideas emerging from their research labs. Officials blew the university’s chance to control the Gatorade royalties when they declined to develop a professor’s idea.

The Gatorade story does not stop there and, even though it’s almost 20 years old, this article stands the test of time. I strongly encourage you to read it if the business end of patents and academia interest you or if you would like to develop more insight into the Broad Institute/UC Berkeley situation.

Getting back to the science, there is that pesky matter of diseases crossing over from one species to another. While, Harvard and eGenesis claim a victory in this area, it seems more work needs to be done.

Infections from pigs

An August 29, 2018 University of Alabama at Birmingham news release (also on EurekAlert) by Jeff Hansen, describes the latest chapter in the quest to provide more organs for transplantion,

A shortage of organs for transplantation — including kidneys and hearts — means that many patients die while still on waiting lists. So, research at the University of Alabama at Birmingham and other sites has turned to pig organs as an alternative. [emphasis mine]

Using gene-editing, researchers have modified such organs to prevent rejection, and research with primates shows the modified pig organs are well-tolerated.

An added step is needed to ensure the safety of these inter-species transplants — sensitive, quantitative assays for viruses and other infectious microorganisms in donor pigs that potentially could gain access to humans during transplantation.

The U.S. Food and Drug Administration requires such testing, prior to implantation, of tissues used for xenotransplantation from animals to humans. It is possible — though very unlikely — that an infectious agent in transplanted tissues could become an emerging infectious disease in humans.

In a paper published in Xenotransplantation, Mark Prichard, Ph.D., and colleagues at UAB have described the development and testing of 30 quantitative assays for pig infectious agents. These assays had sensitivities similar to clinical lab assays for viral loads in human patients. After validation, the UAB team also used the assays on nine sows and 22 piglets delivered from the sows through caesarian section.

“Going forward, ensuring the safety of these organs is of paramount importance,” Prichard said. “The use of highly sensitive techniques to detect potential pathogens will help to minimize adverse events in xenotransplantation.”

“The assays hold promise as part of the screening program to identify suitable donor animals, validate and release transplantable organs for research purposes, and monitor transplant recipients,” said Prichard, a professor in the UAB Department of Pediatrics and director of the Department of Pediatrics Molecular Diagnostics Laboratory.

The UAB researchers developed quantitative polymerase chain reaction, or qPCR, assays for 28 viruses sometimes found in pigs and two groups of mycoplasmas. They established reproducibility, sensitivity, specificity and lower limit of detection for each assay. All but three showed features of good quantitative assays, and the lower limit of detection values ranged between one and 16 copies of the viral or bacterial genetic material.

Also, the pig virus assays did not give false positives for some closely related human viruses.

As a start to understanding the infectious disease load in normal healthy animals and ensuring the safety of pig tissues used in xenotransplantation research, the researchers then screened blood, nasal swab and stool specimens from nine adult sows and 22 of their piglets delivered by caesarian section.

Mycoplasma species and two distinct herpesviruses were the most commonly detected microorganisms. Yet 14 piglets that were delivered from three sows infected with either or both herpesviruses were not infected with the herpesviruses, showing that transmission of these viruses from sow to the caesarian-delivery piglet was inefficient.

Prichard says the assays promise to enhance the safety of pig tissues for xenotransplantation, and they will also aid evaluation of human specimens after xenotransplantation.

The UAB researchers say they subsequently have evaluated more than 300 additional specimens, and that resulted in the detection of most of the targets. “The detection of these targets in pig specimens provides reassurance that the analytical methods are functioning as designed,” said Prichard, “and there is no a priori reason some targets might be more difficult to detect than others with the methods described here.”

As is my custom, here’s a link to and a citation for the paper,

Xenotransplantation panel for the detection of infectious agents in pigs by Caroll B. Hartline, Ra’Shun L. Conner, Scott H. James, Jennifer Potter, Edward Gray, Jose Estrada, Mathew Tector, A. Joseph Tector, Mark N. Prichard. Xenotransplantaion Volume 25, Issue 4 July/August 2018 e12427 DOI: https://doi.org/10.1111/xen.12427 First published: 18 August 2018

This paper is open access.

All this leads to questions about chimeras. If a pig is incubating organs with human cells it’s a chimera but then means the human receiving the organ becomes a chimera too. (For an example, see my Dec. 22, 2013 posting where there’s mention of a woman who received a trachea from a pig. Scroll down about 30% of the way.)

What is it to be human?

A question much beloved of philosophers and others, the question seems particularly timely with xenotransplantion and other developments such neuroprosthetics (cyborgs) and neuromorphic computing (brainlike computing).

As I’ve noted before, although not recently, popular culture offers a discourse on these issues. Take a look at the superhero movies and the way in which enhanced humans and aliens are presented. For example, X-Men comics and movies present mutants (humans with enhanced abilities) as despised and rejected. Video games (not really my thing but there is the Deus Ex series which has as its hero, a cyborg also offer insight into these issues.

Other than popular culture and in the ‘bleeding edge’ arts community, I can’t recall any public discussion on these matters arising from the extraordinary set of technologies which are being deployed or prepared for deployment in the foreseeable future.

(If you’re in Vancouver (Canada) from September 14 – December 15, 2018, you may want to check out Piccinini’s work. Also, there’s ” NCSU [North Carolina State University] Libraries, NC State’s Genetic Engineering and Society (GES) Center, and the Gregg Museum of Art & Design have issued a public call for art for the upcoming exhibition Art’s Work in the Age of Biotechnology: Shaping our Genetic Futures.” from my Sept. 6, 2018 posting. Deadline: Oct. 1, 2018.)

At a guess, there will be pushback from people who have no interest in debating what it is to be human as they already know, and will find these developments, when they learn about them, to be horrifying and unnatural.

Graphene-based neural probes

I have two news bits (dated almost one month apart) about the use of graphene in neural probes, one from the European Union and the other from Korea.

European Union (EU)

This work is being announced by the European Commission’s (a subset of the EU) Graphene Flagship (one of two mega-funding projects announced in 2013; 1B Euros each over ten years for the Graphene Flagship and the Human Brain Project).

According to a March 27, 2017 news item on ScienceDaily, researchers have developed a graphene-based neural probe that has been tested on rats,

Measuring brain activity with precision is essential to developing further understanding of diseases such as epilepsy and disorders that affect brain function and motor control. Neural probes with high spatial resolution are needed for both recording and stimulating specific functional areas of the brain. Now, researchers from the Graphene Flagship have developed a new device for recording brain activity in high resolution while maintaining excellent signal to noise ratio (SNR). Based on graphene field-effect transistors, the flexible devices open up new possibilities for the development of functional implants and interfaces.

The research, published in 2D Materials, was a collaborative effort involving Flagship partners Technical University of Munich (TU Munich; Germany), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS; Spain), Spanish National Research Council (CSIC; Spain), The Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN; Spain) and the Catalan Institute of Nanoscience and Nanotechnology (ICN2; Spain).

Caption: Graphene transistors integrated in a flexible neural probe enables electrical signals from neurons to be measured with high accuracy and density. Inset: The tip of the probe contains 16 flexible graphene transistors. Credit: ICN2

A March 27, 2017 Graphene Flagship press release on EurekAlert, which originated the news item, describes the work,  in more detail,

The devices were used to record the large signals generated by pre-epileptic activity in rats, as well as the smaller levels of brain activity during sleep and in response to visual light stimulation. These types of activities lead to much smaller electrical signals, and are at the level of typical brain activity. Neural activity is detected through the highly localised electric fields generated when neurons fire, so densely packed, ultra-small measuring devices is important for accurate brain readings.

The neural probes are placed directly on the surface of the brain, so safety is of paramount importance for the development of graphene-based neural implant devices. Importantly, the researchers determined that the graphene-based probes are non-toxic, and did not induce any significant inflammation.

Devices implanted in the brain as neural prosthesis for therapeutic brain stimulation technologies and interfaces for sensory and motor devices, such as artificial limbs, are an important goal for improving quality of life for patients. This work represents a first step towards the use of graphene in research as well as clinical neural devices, showing that graphene-based technologies can deliver the high resolution and high SNR needed for these applications.

First author Benno Blaschke (TU Munich) said “Graphene is one of the few materials that allows recording in a transistor configuration and simultaneously complies with all other requirements for neural probes such as flexibility, biocompability and chemical stability. Although graphene is ideally suited for flexible electronics, it was a great challenge to transfer our fabrication process from rigid substrates to flexible ones. The next step is to optimize the wafer-scale fabrication process and improve device flexibility and stability.”

Jose Antonio Garrido (ICN2), led the research. He said “Mechanical compliance is an important requirement for safe neural probes and interfaces. Currently, the focus is on ultra-soft materials that can adapt conformally to the brain surface. Graphene neural interfaces have shown already great potential, but we have to improve on the yield and homogeneity of the device production in order to advance towards a real technology. Once we have demonstrated the proof of concept in animal studies, the next goal will be to work towards the first human clinical trial with graphene devices during intraoperative mapping of the brain. This means addressing all regulatory issues associated to medical devices such as safety, biocompatibility, etc.”

Caption: The graphene-based neural probes were used to detect rats’ responses to visual stimulation, as well as neural signals during sleep. Both types of signals are small, and typically difficult to measure. Credit: ICN2

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

Mapping brain activity with flexible graphene micro-transistors by Benno M Blaschke, Núria Tort-Colet, Anton Guimerà-Brunet, Julia Weinert, Lionel Rousseau, Axel Heimann, Simon Drieschner, Oliver Kempski, Rosa Villa, Maria V Sanchez-Vives. 2D Materials, Volume 4, Number 2 DOI https://doi.org/10.1088/2053-1583/aa5eff Published 24 February 2017

© 2017 IOP Publishing Ltd

This paper is behind a paywall.

Korea

While this research from Korea was published more recently, the probe itself has not been subjected to in vivo (animal testing). From an April 19, 2017 news item on ScienceDaily,

Electrodes placed in the brain record neural activity, and can help treat neural diseases like Parkinson’s and epilepsy. Interest is also growing in developing better brain-machine interfaces, in which electrodes can help control prosthetic limbs. Progress in these fields is hindered by limitations in electrodes, which are relatively stiff and can damage soft brain tissue.

Designing smaller, gentler electrodes that still pick up brain signals is a challenge because brain signals are so weak. Typically, the smaller the electrode, the harder it is to detect a signal. However, a team from the Daegu Gyeongbuk Institute of Science & Technology [DGIST} in Korea developed new probes that are small, flexible and read brain signals clearly.

This is a pretty interesting way to illustrate the research,

Caption: Graphene and gold make a better brain probe. Credit: DGIST

An April 19, 2017 DGIST press release (also on EurekAlert), which originated the news item, expands on the theme (Note: A link has been removed),

The probe consists of an electrode, which records the brain signal. The signal travels down an interconnection line to a connector, which transfers the signal to machines measuring and analysing the signals.

The electrode starts with a thin gold base. Attached to the base are tiny zinc oxide nanowires, which are coated in a thin layer of gold, and then a layer of conducting polymer called PEDOT. These combined materials increase the probe’s effective surface area, conducting properties, and strength of the electrode, while still maintaining flexibility and compatibility with soft tissue.

Packing several long, thin nanowires together onto one probe enables the scientists to make a smaller electrode that retains the same effective surface area of a larger, flat electrode. This means the electrode can shrink, but not reduce signal detection. The interconnection line is made of a mix of graphene and gold. Graphene is flexible and gold is an excellent conductor. The researchers tested the probe and found it read rat brain signals very clearly, much better than a standard flat, gold electrode.

“Our graphene and nanowires-based flexible electrode array can be useful for monitoring and recording the functions of the nervous system, or to deliver electrical signals to the brain,” the researchers conclude in their paper recently published in the journal ACS Applied Materials and Interfaces.

The probe requires further clinical tests before widespread commercialization. The researchers are also interested in developing a wireless version to make it more convenient for a variety of applications.

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

Enhancement of Interface Characteristics of Neural Probe Based on Graphene, ZnO Nanowires, and Conducting Polymer PEDOT by Mingyu Ryu, Jae Hoon Yang, Yumi Ahn, Minkyung Sim, Kyung Hwa Lee, Kyungsoo Kim, Taeju Lee, Seung-Jun Yoo, So Yeun Kim, Cheil Moon, Minkyu Je, Ji-Woong Choi, Youngu Lee, and Jae Eun Jang. ACS Appl. Mater. Interfaces, 2017, 9 (12), pp 10577–10586 DOI: 10.1021/acsami.7b02975 Publication Date (Web): March 7, 2017

Copyright © 2017 American Chemical Society

This paper is behind a paywall.

The memristor as the ‘missing link’ in bioelectronic medicine?

The last time I featured memrisors and a neuronal network it was in an April 22, 2016 posting about Russian research in that field. This latest work comes from the UK’s University of Southampton. From a Sept. 27, 2016 news item on phys.org,

New research, led by the University of Southampton, has demonstrated that a nanoscale device, called a memristor, could be the ‘missing link’ in the development of implants that use electrical signals from the brain to help treat medical conditions.

Monitoring neuronal cell activity is fundamental to neuroscience and the development of neuroprosthetics – biomedically engineered devices that are driven by neural activity. However, a persistent problem is the device being able to process the neural data in real-time, which imposes restrictive requirements on bandwidth, energy and computation capacity.

In a new study, published in Nature Communications, the researchers showed that memristors could provide real-time processing of neuronal signals (spiking events) leading to efficient data compression and the potential to develop more precise and affordable neuroprosthetics and bioelectronic medicines.

A Sept. 27, 2016 University of Southampton press release, which originated the news item, expands on the theme,

Memristors are electrical components that limit or regulate the flow of electrical current in a circuit and can remember the amount of charge that was flowing through it and retain the data, even when the power is turned off.

Lead author Isha Gupta, Postgraduate Research Student at the University of Southampton, said: “Our work can significantly contribute towards further enhancing the understanding of neuroscience, developing neuroprosthetics and bio-electronic medicines by building tools essential for interpreting the big data in a more effective way.”

The research team developed a nanoscale Memristive Integrating Sensor (MIS) into which they fed a series of voltage-time samples, which replicated neuronal electrical activity.

Acting like synapses in the brain, the metal-oxide MIS was able to encode and compress (up to 200 times) neuronal spiking activity recorded by multi-electrode arrays. Besides addressing the bandwidth constraints, this approach was also very power efficient – the power needed per recording channel was up to 100 times less when compared to current best practice.

Co-author Dr Themis Prodromakis, Reader in Nanoelectronics and EPSRC Fellow in Electronics and Computer Science at the University of Southampton said: “We are thrilled that we succeeded in demonstrating that these emerging nanoscale devices, despite being rather simple in architecture, possess ultra-rich dynamics that can be harnessed beyond the obvious memory applications to address the fundamental constraints in bandwidth and power that currently prohibit scaling neural interfaces beyond 1,000 recording channels.”

The Prodromakis Group at the University of Southampton is acknowledged as world-leading in this field, collaborating among others with Leon Chua (a Diamond Jubilee Visiting Academic at the University of Southampton), who theoretically predicted the existence of memristors in 1971.

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

Real-time encoding and compression of neuronal spikes by metal-oxide memristors by Isha Gupta, Alexantrou Serb, Ali Khiat, Ralf Zeitler, Stefano Vassanelli, & Themistoklis Prodromakis. Nature Communications 7, Article number: 12805 doi:10.1038/ncomms12805 Published  26 September 2016

This is an open access paper.

For anyone who’s interested in better understanding memristors, there’s an interview with Forrest H Bennett III in my April 7, 2010 posting and you can always check Wikipedia.

Biohackers (also known as bodyhackers or grinders) become more common?

Stephen Melendez’s June 11, 2016 story about biohackers/bodyhackers/grinders for Fast Company sports a striking image in the banner, an x-ray of a pair hands featuring some mysterious additions to the webbing between thumbs and forefingers (Note: Links have been removed),

Tim Shank can guarantee he’ll never leave home without his keys. Why? His house keys are located inside his body.

Shank, the president of the Minneapolis futurist group TwinCities+, has a chip installed in his hand that can communicate electronically with his front door and tell it to unlock itself. His wife has one, too.

In fact, Shank has several chips in his hand, including a near field communication (NFC) chip like the ones used in Apple Pay and similar systems, which stores a virtual business card with contact information for TwinCities+. “[For] people with Android phones, I can just tap their phone with my hand, right over the chip, and it will send that information to their phone,” he says. In the past, he’s also used a chip to store a bitcoin wallet.

Shank is one of a growing number of “biohackers” who implant hardware ranging from microchips to magnets inside their bodies.

Certainly the practice seems considerably more developed since the first time it was mentioned here in a May 27, 2010 posting about a researcher who’d implanted a chip into his body which he then contaminated with a computer virus. In the comments, you’ll find Amal Grafstraa who’s mentioned in the Melendez article at some length, from the Melendez article (Note: Links have been removed),

Some biohackers use their implants in experimental art projects. Others who have disabilities or medical conditions use them to improve their quality of life, while still others use the chips to extend the limits of human perception. …

Experts sometimes caution that the long-term health risks of the practice are still unknown. But many biohackers claim that, if done right, implants can be no more dangerous than getting a piercing or tattoo. In fact, professional body piercers are frequently the ones tasked with installing these implants, given that they possess the training and sterilization equipment necessary to break people’s skin safely.

“When you talk about things like risk, things like putting it in your body, the reality is the risk of having one of these installed is extremely low—it’s even lower than an ear piercing,” claims Amal Graafstra, the founder of Dangerous Things, a biohacking supply company.

Graafstra, who is also the author of the book RFID Toys, says he first had an RFID chip installed in his hand in 2005, which allowed him to unlock doors without a key. When the maker movement took off a few years later, and as more hackers began to explore what they could put inside their bodies, he founded Dangerous Things with the aim of ensuring these procedures were done safely.

“I decided maybe it’s time to wrap a business model around this and make sure that the things people are trying to put in their bodies are safe,” he says. The company works with a network of trained body piercers and offers online manuals and videos for piercers looking to get up to speed on the biohacking movement.

At present, these chips are capable of verifying users’ identities and opening doors. And according to Graafstra, a next-generation chip will have enough on-board cryptographic power to potentially work with credit card terminals securely.

“The technology is there—we can definitely talk to payment terminals with it—but we don’t have the agreements in place with banks [and companies like] MasterCard to make that happen,” he says.

Paying for goods with an implantable chip might sound unusual for consumers and risky for banks, but Graafstra thinks the practice will one day become commonplace. He points to a survey released by Visa last year that found that 25% of Australians are “at least slightly interested” in paying for purchases through a chip implanted in their bodies.

Melendez’s article is fascinating and well worth reading in its entirety. It’s not all keys and commerce as this next and last excerpt shows,

Other implantable technology has more of an aesthetic focus: Pittsburgh biohacking company Grindhouse Wetware offers a below-the-skin, star-shaped array of LED lights called Northstar. While the product was inspired by the on-board lamps of a device called Circadia that Grindhouse founder Tim Cannon implanted to send his body temperature to a smartphone, the commercially available Northstar features only the lights and is designed to resemble natural bioluminescence.

“This particular device is mainly aesthetic,” says Grindhouse spokesman Ryan O’Shea. “It can backlight tattoos or be used in any kind of interpretive dance, or artists can use it in various ways.”

The lights activate in the presence of a magnetic field—one that is often provided by magnets already implanted in the same user’s fingertips. Which brings up another increasingly common piece of bio-hardware: magnetic finger implants. ….

There are other objects that can be implanted in bodies. In one case, an artist, Wafaa Bilal had a camera implanted into the back of his head for a 3rd eye. I mentioned the Iraqi artist in my April 13, 2011 posting titled: Blood, memristors, cyborgs plus brain-controlled computers, prosthetics, and art (scroll down about 75% of the way). Bilal was unable to find a doctor who would perform the procedure so he went to a body-piercing studio. Unfortunately, the posting chronicles his infection and subsequent removal of the camera (h/t Feb. 11, 2011 BBC [British Broadcasting Corporation] news online article).

Observations

It’s been a while since I’ve written about bodyhacking and I’d almost forgotten about the practice relegating it to the category of “one of those trendy ideas that get left behind as interest shifts.” My own interest had shifted more firmly to neuroprosthetics (the integration of prostheses into the nervous system).

I had coined a tag for bodyhacking and neuroprostheses: machine/flesh which covers both those topics and more (e.g. cyborgs) as we continue to integrate machines into our bodies.

Final note

I was reminded of Wafaa Bilal recently when checking out a local arts magazine, Preview: the gallery guide, June/July/August 2016 issue. His work (the 168:01show) is being shown in Calgary, Alberta, Canada at the Esker Foundation from May 27 to August 28, 2016,

168:01 is a major solo exhibition of new and recent work by Iraqi-born, New York-based artist Wafaa Bilal, renowned for his online performances and technologically driven encounters that speak to the impact of international politics on individual lives.

In 168:01, Bilal takes the Bayt al-Hikma, or House of Wisdom, as a starting point for a sculptural installation of a library. The Bayt al-Hikma was a major academic center during the Islamic Golden Age where Muslim, Jewish, and Christian scholars studied the humanities and science. By the middle of the Ninth Century, the House of Wisdom had accumulated the largest library in the world. Four centuries later, a Mongol siege laid waste to all the libraries of Baghdad along with the House of Wisdom. According to some accounts, the library was thrown into the Tigris River to create a bridge of books for the Mongol army to cross. The pages bled ink into the river for seven days – or 168 hours, after which the books were drained of knowledge. Today, the Bayt al-Hikma represents one of the most well-known examples of historic cultural loss as a casualty of wartime.

For this exhibition, Bilal has constructed a makeshift library filled with empty white books. The white books symbolize the priceless cultural heritage destroyed at Bayt al-Hikma as well as the libraries, archives, and museums whose systematic decimation by occupying forces continues to ravage his homeland. Throughout the duration of the exhibition, the white books will slowly be replaced with visitor donations from a wishlist compiled by The College of Fine Arts at the University of Baghdad, whose library was looted and destroyed in 2003. At the end of each week a volunteer unpacks the accumulated shipments, catalogues each new book by hand, and places the books on the shelves. At the end of the exhibition, all the donated books will be sent to the University of Baghdad to help rebuild their library. This exchange symbolizes the power of individuals to rectify violence inflicted on cultural spaces that are meant to preserve and store knowledge for future generations.

In conjunction with the library, Bilal presents a powerful suite of photographs titled The Ashes Series that brings the viewer closer to images of violence and war in the Middle East. In an effort to foster empathy and humanize the onslaught of violent images that inundate Western media during wartime, Bilal has reconstructed journalistic images of the destruction caused by the Iraq War. He writes, “Reconstructing the destructed spaces is a way to exist in them, to share them with an audience, and to provide a layer of distance, as the original photographs are too violent and run the risk of alienating the viewer. It represents an attempt to make sense of the destruction and to preserve the moment of serenity after the dust has settled, to give the ephemeral moment extended life in a mix of beauty and violence.” In the photograph Al-Mutanabbi Street from The Ashes Series, the viewer encounters dilapidated historic and modern buildings on a street covered with layers upon layers of rubble and fragments of torn books. Bilal’s images emanate a slowness that deepens engagement between the viewer and the image, thereby inviting them to share the burden of obliterated societies and reimagine a world built on the values of peace and hope.

The House of Wisdom has been mentioned here a few times perhaps most comprehensively and in the context of the then recent opening of the King Abdullah University for Science and Technology (KAUST; located in Saudi Arabia) in this Sept. 24, 2009 posting (scroll down about 45% of the way).

Anyone interested in hacking their own body?

 

I expect you can find out more Amal Grafstraa’s website.

Sinagpore’s new chip could make low-powered wireless neural implants a possibility and Australians develop their own neural implant

Singapore

This research from Singapore could make neuroprosthetics and exoskeletons a little easier to manage as long as you don’t mind having a neural implant. From a Feb. 11, 2016 news item on ScienceDaily,

A versatile chip offers multiple applications in various electronic devices, report researchers, suggested that there is now hope that a low-powered, wireless neural implant may soon be a reality. Neural implants when embedded in the brain can alleviate the debilitating symptoms of Parkinson’s disease or give paraplegic people the ability to move their prosthetic limbs.

Caption: NTU Asst Prof Arindam Basu is holding his low-powered smart chip. Credit: NTU Singapore

Caption: NTU Asst Prof Arindam Basu is holding his low-powered smart chip. Credit: NTU Singapore

A Feb. 11, 2016 Nanyang Technological University (NTU) press release (also on EurekAlert), which originated the news item, provides more detail,

Scientists at Nanyang Technological University, Singapore (NTU Singapore) have developed a small smart chip that can be paired with neural implants for efficient wireless transmission of brain signals.

Neural implants when embedded in the brain can alleviate the debilitating symptoms of Parkinson’s disease or give paraplegic people the ability to move their prosthetic limbs.

However, they need to be connected by wires to an external device outside the body. For a prosthetic patient, the neural implant is connected to a computer that decodes the brain signals so the artificial limb can move.

These external wires are not only cumbersome but the permanent openings which allow the wires into the brain increases the risk of infections.

The new chip by NTU scientists can allow the transmission of brain data wirelessly and with high accuracy.

Assistant Professor Arindam Basu from NTU’s School of Electrical and Electronic Engineering said the research team have tested the chip on data recorded from animal models, which showed that it could decode the brain’s signal to the hand and fingers with 95 per cent accuracy.

“What we have developed is a very versatile smart chip that can process data, analyse patterns and spot the difference,” explained Prof Basu.

“It is about a hundred times more efficient than current processing chips on the market. It will lead to more compact medical wearable devices, such as portable ECG monitoring devices and neural implants, since we no longer need large batteries to power them.”

Different from other wireless implants

To achieve high accuracy in decoding brain signals, implants require thousands of channels of raw data. To wirelessly transmit this large amount of data, more power is also needed which means either bigger batteries or more frequent recharging.

This is not feasible as there is limited space in the brain for implants while frequent recharging means the implants cannot be used for long-term recording of signals.

Current wireless implant prototypes thus suffer from a lack of accuracy as they lack the bandwidth to send out thousands of channels of raw data.

Instead of enlarging the power source to support the transmission of raw data, Asst Prof Basu tried to reduce the amount of data that needs to be transmitted.

Designed to be extremely power-efficient, NTU’s patented smart chip will analyse and decode the thousands of signals from the neural implants in the brain, before compressing the results and sending it wirelessly to a small external receiver.

This invention and its findings were published last month [December 2015] in the prestigious journal, IEEE Transactions on Biomedical Circuits & Systems, by the Institute of Electrical and Electronics Engineers, the world’s largest professional association for the advancement of technology.

Its underlying science was also featured in three international engineering conferences (two in Atlanta, USA and one in China) over the last three months.

Versatile smart chip with multiple uses

This new smart chip is designed to analyse data patterns and spot any abnormal or unusual patterns.

For example, in a remote video camera, the chip can be programmed to send a video back to the servers only when a specific type of car or something out of the ordinary is detected, such as an intruder.

This would be extremely beneficial for the Internet of Things (IOT), where every electrical and electronic device is connected to the Internet through a smart chip.

With a report by marketing research firm Gartner Inc predicting that 6.4 billion smart devices and appliances will be connected to the Internet by 2016, and will rise to 20.8 billion devices by 2020, reducing network traffic will be a priority for most companies.

Using NTU’s new chip, the devices can process and analyse the data on site, before sending back important details in a compressed package, instead of sending the whole data stream. This will reduce data usage by over a thousand times.

Asst Prof Basu is now in talks with Singapore Technologies Electronics Limited to adapt his smart chip that can significantly reduce power consumption and the amount of data transmitted by battery-operated remote sensors, such as video cameras.

The team is also looking to expand the applications of the chip into commercial products, such as to customise it for smart home sensor networks, in collaboration with a local electronics company.

The chip, measuring 5mm by 5mm can now be licensed by companies from NTU’s commercialisation arm, NTUitive.

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

A 128-Channel Extreme Learning Machine-Based Neural Decoder for Brain Machine Interfaces by Yi Chen, Enyi Yao, Arindam Basu. IEEE Transactions on Biomedical Circuits and Systems, 2015; 1 DOI: 10.1109/TBCAS.2015.2483618

This paper is behind a paywall.

Australia

Earlier this month there was a Feb. 9, 2016 announcement about a planned human clinical trial in Australia for a new brain-machine interface (neural implant). Before proceeding with the news, here’s what this implant looks like,

Caption: This tiny device, the size of a small paperclip, is implanted in to a blood vessel next to the brain and can read electrical signals from the motor cortex, the brain's control centre. These signals can then be transmitted to an exoskeleton or wheelchair to give paraplegic patients greater mobility. Users will need to learn how to communicate with their machinery, but over time, it is thought it will become second nature, like driving or playing the piano. The first human trials are slated for 2017 in Melbourne, Australia. Credit: The University of Melbourne.

Caption: This tiny device, the size of a small paperclip, is implanted in to a blood vessel next to the brain and can read electrical signals from the motor cortex, the brain’s control centre. These signals can then be transmitted to an exoskeleton or wheelchair to give paraplegic patients greater mobility. Users will need to learn how to communicate with their machinery, but over time, it is thought it will become second nature, like driving or playing the piano. The first human trials are slated for 2017 in Melbourne, Australia. Credit: The University of Melbourne.

A Feb. 9, 2016 University of Melbourne press release (also on EurekAlert), which originated the news item, provides more detail,

Melbourne medical researchers have created a new minimally invasive brain-machine interface, giving people with spinal cord injuries new hope to walk again with the power of thought.

The brain machine interface consists of a stent-based electrode (stentrode), which is implanted within a blood vessel next to the brain, and records the type of neural activity that has been shown in pre-clinical trials to move limbs through an exoskeleton or to control bionic limbs.

The new device is the size of a small paperclip and will be implanted in the first in-human trial at The Royal Melbourne Hospital in 2017.

The results published today in Nature Biotechnology show the device is capable of recording high-quality signals emitted from the brain’s motor cortex, without the need for open brain surgery.

Principal author and Neurologist at The Royal Melbourne Hospital and Research Fellow at The Florey Institute of Neurosciences and the University of Melbourne, Dr Thomas Oxley, said the stentrode was revolutionary.

“The development of the stentrode has brought together leaders in medical research from The Royal Melbourne Hospital, The University of Melbourne and the Florey Institute of Neuroscience and Mental Health. In total 39 academic scientists from 16 departments were involved in its development,” Dr Oxley said.

“We have been able to create the world’s only minimally invasive device that is implanted into a blood vessel in the brain via a simple day procedure, avoiding the need for high risk open brain surgery.

“Our vision, through this device, is to return function and mobility to patients with complete paralysis by recording brain activity and converting the acquired signals into electrical commands, which in turn would lead to movement of the limbs through a mobility assist device like an exoskeleton. In essence this a bionic spinal cord.”

Stroke and spinal cord injuries are leading causes of disability, affecting 1 in 50 people. There are 20,000 Australians with spinal cord injuries, with the typical patient a 19-year old male, and about 150,000 Australians left severely disabled after stroke.

Co-principal investigator and biomedical engineer at the University of Melbourne, Dr Nicholas Opie, said the concept was similar to an implantable cardiac pacemaker – electrical interaction with tissue using sensors inserted into a vein, but inside the brain.

“Utilising stent technology, our electrode array self-expands to stick to the inside wall of a vein, enabling us to record local brain activity. By extracting the recorded neural signals, we can use these as commands to control wheelchairs, exoskeletons, prosthetic limbs or computers,” Dr Opie said.

“In our first-in-human trial, that we anticipate will begin within two years, we are hoping to achieve direct brain control of an exoskeleton for three people with paralysis.”

“Currently, exoskeletons are controlled by manual manipulation of a joystick to switch between the various elements of walking – stand, start, stop, turn. The stentrode will be the first device that enables direct thought control of these devices”

Neurophysiologist at The Florey, Professor Clive May, said the data from the pre-clinical study highlighted that the implantation of the device was safe for long-term use.

“Through our pre-clinical study we were able to successfully record brain activity over many months. The quality of recording improved as the device was incorporated into tissue,” Professor May said.

“Our study also showed that it was safe and effective to implant the device via angiography, which is minimally invasive compared with the high risks associated with open brain surgery.

“The brain-computer interface is a revolutionary device that holds the potential to overcome paralysis, by returning mobility and independence to patients affected by various conditions.”

Professor Terry O’Brien, Head of Medicine at Departments of Medicine and Neurology, The Royal Melbourne Hospital and University of Melbourne said the development of the stentrode has been the “holy grail” for research in bionics.

“To be able to create a device that can record brainwave activity over long periods of time, without damaging the brain is an amazing development in modern medicine,” Professor O’Brien said.

“It can also be potentially used in people with a range of diseases aside from spinal cord injury, including epilepsy, Parkinsons and other neurological disorders.”

The development of the minimally invasive stentrode and the subsequent pre-clinical trials to prove its effectiveness could not have been possible without the support from the major funding partners – US Defense Department DARPA [Defense Advanced Research Projects Agency] and Australia’s National Health and Medical Research Council.

So, DARPA is helping fund this, eh? Interesting but not a surprise given the agency’s previous investments in brain research and neuroprosthetics.

For those who like to get their news via video,

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

Minimally invasive endovascular stent-electrode array for high-fidelity, chronic recordings of cortical neural activity by Thomas J Oxley, Nicholas L Opie, Sam E John, Gil S Rind, Stephen M Ronayne, Tracey L Wheeler, Jack W Judy, Alan J McDonald, Anthony Dornom, Timothy J H Lovell, Christopher Steward, David J Garrett, Bradford A Moffat, Elaine H Lui, Nawaf Yassi, Bruce C V Campbell, Yan T Wong, Kate E Fox, Ewan S Nurse, Iwan E Bennett, Sébastien H Bauquier, Kishan A Liyanage, Nicole R van der Nagel, Piero Perucca, Arman Ahnood et al. Nature Biotechnology (2016)  doi:10.1038/nbt.3428 Published online 08 February 2016

This paper is behind a paywall.

I wish the researchers in Singapore, Australia, and elsewhere, good luck!

Nanotechnology and cybersecurity risks

Gregory Carpenter has written a gripping (albeit somewhat exaggerated) piece for Signal, a publication of the  Armed Forces Communications and Electronics Association (AFCEA) about cybersecurity issues and  nanomedicine endeavours. From Carpenter’s Jan. 1, 2016 article titled, When Lifesaving Technology Can Kill; The Cyber Edge,

The exciting advent of nanotechnology that has inspired disruptive and lifesaving medical advances is plagued by cybersecurity issues that could result in the deaths of people that these very same breakthroughs seek to heal. Unfortunately, nanorobotic technology has suffered from the same security oversights that afflict most other research and development programs.

Nanorobots, or small machines [or nanobots[, are vulnerable to exploitation just like other devices.

At the moment, the issue of cybersecurity exploitation is secondary to making nanobots, or nanorobots, dependably functional. As far as I’m aware, there is no such nanobot. Even nanoparticles meant to function as packages for drug delivery have not been perfected (see one of the controversies with nanomedicine drug delivery described in my Nov. 26, 2015 posting).

That said, Carpenter’s point about cybersecurity is well taken since security features are often overlooked in new technology. For example, automated banking machines (ABMs) had woefully poor (inadequate, almost nonexistent) security when they were first introduced.

Carpenter outlines some of the problems that could occur, assuming some of the latest research could be reliably  brought to market,

The U.S. military has joined the fray of nanorobotic experimentation, embarking on revolutionary research that could lead to a range of discoveries, from unraveling the secrets of how brains function to figuring out how to permanently purge bad memories. Academia is making amazing advances as well. Harnessing progress by Harvard scientists to move nanorobots within humans, researchers at the University of Montreal, Polytechnique Montreal and Centre Hospitalier Universitaire Sainte-Justine are using mobile nanoparticles inside the human brain to open the blood-brain barrier, which protects the brain from toxins found in the circulatory system.

A different type of technology presents a risk similar to the nanoparticles scenario. A DARPA-funded program known as Restoring Active Memory (RAM) addresses post-traumatic stress disorder, attempting to overcome memory deficits by developing neuroprosthetics that bridge gaps in an injured brain. In short, scientists can wipe out a traumatic memory, and they hope to insert a new one—one the person has never actually experienced. Someone could relish the memory of a stroll along the French Riviera rather than a terrible firefight, even if he or she has never visited Europe.

As an individual receives a disruptive memory, a cyber criminal could manage to hack the controls. Breaches of the brain could become a reality, putting humans at risk of becoming zombie hosts [emphasis mine] for future virus deployments. …

At this point, the ‘zombie’ scenario Carpenter suggests seems a bit over-the-top but it does hearken to the roots of the zombie myth where the undead aren’t mindlessly searching for brains but are humans whose wills have been overcome. Mike Mariani in an Oct. 28, 2015 article for The Atlantic has presented a thought-provoking history of zombies,

… the zombie myth is far older and more rooted in history than the blinkered arc of American pop culture suggests. It first appeared in Haiti in the 17th and 18th centuries, when the country was known as Saint-Domingue and ruled by France, which hauled in African slaves to work on sugar plantations. Slavery in Saint-Domingue under the French was extremely brutal: Half of the slaves brought in from Africa were worked to death within a few years, which only led to the capture and import of more. In the hundreds of years since, the zombie myth has been widely appropriated by American pop culture in a way that whitewashes its origins—and turns the undead into a platform for escapist fantasy.

The original brains-eating fiend was a slave not to the flesh of others but to his own. The zombie archetype, as it appeared in Haiti and mirrored the inhumanity that existed there from 1625 to around 1800, was a projection of the African slaves’ relentless misery and subjugation. Haitian slaves believed that dying would release them back to lan guinée, literally Guinea, or Africa in general, a kind of afterlife where they could be free. Though suicide was common among slaves, those who took their own lives wouldn’t be allowed to return to lan guinée. Instead, they’d be condemned to skulk the Hispaniola plantations for eternity, an undead slave at once denied their own bodies and yet trapped inside them—a soulless zombie.

I recommend reading Mariani’s article although I do have one nit to pick. I can’t find a reference to brain-eating zombies until George Romero’s introduction of the concept in his movies. This Zombie Wikipedia entry seems to be in agreement with my understanding (if I’m wrong, please do let me know and, if possible, provide a link to the corrective text).

Getting back to Carpenter and cybersecurity with regard to nanomedicine, while his scenarios may seem a trifle extreme it’s precisely the kind of thinking you need when attempting to anticipate problems. I do wish he’d made clear that the technology still has a ways to go.

Better neuroprostheses for brain diseases and mental illneses

I don’t often get news releases from Sweden but I do on occasion and, sometimes, they even come in their original Swedish versions. In this case, Lund University sent me an English language version about their latest work making brain implants (neural prostheses) safer and effective. From a Sept. 29, 2015 Lund University news release (also on EurekAlert),

Neurons thrive and grow in a new type of nanowire material developed by researchers in Nanophysics and Ophthalmology at Lund University in Sweden. In time, the results might improve both neural and retinal implants, and reduce the risk of them losing their effectiveness over time, which is currently a problem

By implanting electrodes in the brain tissue one can stimulate or capture signals from different areas of the brain. These types of brain implants, or neuro-prostheses as they are sometimes called, are used to treat Parkinson’s disease and other neurological diseases.

They are currently being tested in other areas, such as depression, severe cases of autism, obsessive-compulsive disorders and paralysis. Another research track is to determine whether retinal implants are able to replace light-sensitive cells that die in cases of Retinitis Pigmentosa and other eye diseases.

However, there are severe drawbacks associated with today’s implants. One problem is that the body interprets the implants as foreign objects, resulting in an encapsulation of the electrode, which in turn leads to loss of signal.

One of the researchers explains the approach adopted by the research team (from the news release),

“Our nanowire structure prevents the cells that usually encapsulate the electrodes – glial cells – from doing so”, says Christelle Prinz, researcher in Nanophysics at Lund University in Sweden, who developed this technique together with Maria Thereza Perez, a researcher in Ophthalmology.

“I was very pleasantly surprised by these results. In previous in-vitro experiments, the glial cells usually attach strongly to the electrodes”, she says.

To avoid this, the researchers have developed a small substrate where regions of super thin nanowires are combined with flat regions. While neurons grow and extend processes on the nanowires, the glial cells primarily occupy the flat regions in between.

“The different types of cells continue to interact. This is necessary for the neurons to survive because the glial cells provide them with important molecules.”

So far, tests have only been done with cultured cells (in vitro) but hopefully they will soon be able to continue with experiments in vivo.

The substrate is made from the semiconductor material gallium phosphide where each outgrowing nanowire has a diameter of only 80 nanometres (billionths of a metre).

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

Support of Neuronal Growth Over Glial Growth and Guidance of Optic Nerve Axons by Vertical Nanowire Arrays by Gaëlle Piret, Maria-Thereza Perez, and Christelle N. Prinz. ACS Appl. Mater. Interfaces, 2015, 7 (34), pp 18944–18948 DOI: 10.1021/acsami.5b03798 Publication Date (Web): August 11, 2015

Copyright © 2015 American Chemical Society

This paper appears to be open access as I was able to link to the PDF version.

Brain-friendly interface to replace neural prosthetics one day?

This research will not find itself occupying anyone’s brain for some time to come but it is interesting to find out that neural prosthetics have some drawbacks and there is work being done to address them. From an Aug. 10, 2015 news item on Azonano,

Instead of using neural prosthetic devices–which suffer from immune-system rejection and are believed to fail due to a material and mechanical mismatch–a multi-institutional team, including Lohitash Karumbaiah of the University of Georgia’s Regenerative Bioscience Center, has developed a brain-friendly extracellular matrix environment of neuronal cells that contain very little foreign material. These by-design electrodes are shielded by a covering that the brain recognizes as part of its own composition.

An Aug. 5, 2015 University of Georgia news release, which originated the news item, describes the new approach and technique in more detail,

Although once believed to be devoid of immune cells and therefore of immune responses, the brain is now recognized to have its own immune system that protects it against foreign invaders.

“This is not by any means the device that you’re going to implant into a patient,” said Karumbaiah, an assistant professor of animal and dairy science in the UGA College of Agricultural and Environmental Sciences. “This is proof of concept that extracellular matrix can be used to ensheathe a functioning electrode without the use of any other foreign or synthetic materials.”

Implantable neural prosthetic devices in the brain have been around for almost two decades, helping people living with limb loss and spinal cord injury become more independent. However, not only do neural prosthetic devices suffer from immune-system rejection, but most are believed to eventually fail because of a mismatch between the soft brain tissue and the rigid devices.

The collaboration, led by Wen Shen and Mark Allen of the University of Pennsylvania, found that the extracellular matrix derived electrodes adapted to the mechanical properties of brain tissue and were capable of acquiring neural recordings from the brain cortex.

“Neural interface technology is literally mind boggling, considering that one might someday control a prosthetic limb with one’s own thoughts,” Karumbaiah said.

The study’s joint collaborators were Ravi Bellamkonda, who conceived the new approach and is chair of the Wallace H. Coulter Department of Biomedical Engineering at the Georgia Institute of Technology and Emory University, as well as Allen, who at the time was director of the Institute for Electronics and Nanotechnology.

“Hopefully, once we converge upon the nanofabrication techniques that would enable these to be clinically translational, this same methodology could then be applied in getting these extracellular matrix derived electrodes to be the next wave of brain implants,” Karumbaiah said.

Currently, one out of every 190 Americans is living with limb loss, according to the National Institutes of Health. There is a significant burden in cost of care and quality of life for people suffering from this disability.

The research team is one part of many in the prosthesis industry, which includes those who design the robotics for the artificial limbs, others who make the neural prosthetic devices and developers who design the software that decodes the neural signal.

“What neural prosthetic devices do is communicate seamlessly to an external prosthesis,” Karumbaiah said, “providing independence of function without having to have a person or a facility dedicated to their care.”

Karumbaiah hopes further collaboration will allow them to make positive changes in the industry, saying that, “it’s the researcher-to-industry kind of conversation that now needs to take place, where companies need to come in and ask: ‘What have you learned? How are the devices deficient, and how can we make them better?'”

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

Extracellular matrix-based intracortical microelectrodes: Toward a microfabricated neural interface based on natural materials by Wen Shen, Lohitash Karumbaiah, Xi Liu, Tarun Saxena, Shuodan Chen, Radhika Patkar, Ravi V. Bellamkonda, & Mark G. Allen. Microsystems & Nanoengineering 1, Article number: 15010 (2015) doi:10.1038/micronano.2015.10

This appears to be an open access paper.

One final note, I have written frequently about prosthetics and neural prosthetics, which you can find by using either of those terms and/or human enhancement. Here’s my latest piece, a March 25, 2015 posting.

Metallic nanoflowers produce neuron-like fractals

I was a bit surprised to find that this University of Oregon story was about a patent. Here’s more from a July 28, 2015 news item on Azonano,

Richard Taylor’s vision of using artificial fractal-based implants to restore sight to the blind — part of a far-reaching concept that won an innovation award this year from the White House — is now covered under a broad U.S. patent.

The patent goes far beyond efforts to use the emerging technology to restore eyesight. It covers all fractal-designed electronic implants that link signaling activity with nerves for any purpose in animal and human biology.

Fractals are objects with irregular curves or shapes. “They are a trademark building block of nature,” said Taylor, a professor of physics and director of the Materials Science Institute at the University of Oregon [UO]. “In math, that property is self-similarity. Trees, clouds, rivers, galaxies, lungs and neurons are fractals. What we hope to do is adapt the technology to nature’s geometry.”

Named in U.S. patent 9079017 are Taylor, the UO, Taylor’s research collaborator Simon Brown, and Brown’s home institution, the University of Canterbury in New Zealand.

A July 28, 2015 University of Oregon news release (also on EurekAlert) by Jim Barlow, which originated the news item, continues the patent celebration,

“We’re very delighted,” Taylor said. “The U.S. Patent and Trademark Office has recognized the novelty and utility of our general concept, but there is a lot to do. We want to get all of the fundamental science sorted out. We’re looking at least another couple of years of basic science before moving forward.”

The patent solidifies the relationship between the two universities, said Charles Williams, associate vice president for innovation at the UO. “This is still in the very early days. This project has attracted national attention, awards and grants.

“We hope to engage the right set of partners to develop the technology over time as the concept moves into potentially vast forms of medical applications,” Williams added. “Dr. Taylor’s interdisciplinary science is a hallmark of the creativity at the University of Oregon and a great example of the international research collaborations that our faculty engage in every day.”

Here’s an image illustrating the ‘fractal neurons’,

FractalImplant

Caption: Retinal neurons, outlined in yellow, attach to and follows branches of a fractal interconnect. Such connections, says University of Oregon physicist Richard Taylor, could some day help to treat eye diseases such as macular degeneration. Credit: Courtesy of Richard Taylor

The news release goes on to describe the ‘fractal approach’ to eye implants which is markedly different from the implants entering the marketplace,

Taylor raised the idea of a fractal-based approach to treat eye diseases in a 2011 article in Physics World, writing that it could overcome problems associated with efforts to insert photodiodes behind the eyes. Current chip technology doesn’t allow sufficient connections with neurons.

“The wiring — the neurons — in the retina is fractal, but the chips are not fractal,” Taylor said. His vision, based on research with Brown, is to grow nanoflowers seeded from nanoparticles of metals that self assemble in a natural process, producing fractals that mimic and communicate with neurons.

It is conceivable, Taylor said, that fractal interconnects — as the implants are called in the patent — could be shaped so they network with like-shaped neurons to address narrow needs, such as a feedback loop for the sensation of touch from a prosthetic arm or leg to the brain.

Such implants would overcome the biological rejection of implants with smooth surfaces or those randomly patterned that have been developed in a trial-and-error approach to link to neurons.

Once perfected, he said, the implants would generate an electrical field that would fool a sea of glial cells that insulate and protect neurons from foreign invaders. Fractal interconnects would allow electrical signals to operate in “a safety zone biologically” that avoids toxicity issues.

“The patent covers any generic interface for connecting any electronics to any nerve,” Taylor said, adding that fractal interconnects are not electrodes. “Our interface is multifunctional. The primary thing is to get the electrical field into the system so that reaches the neurons and induces the signal.”

Taylor’s proposal for using fractal-based technology earned the top prize in a contest held by the innovation company InnoCentive. Taylor was honored in April [2015] at a meeting of the White House Office of Science and Technology Policy.

The competition was sponsored by a collaboration of science philanthropies including the Research Corporation for Science Advancement, the Gordon and Betty Moore Foundation, the W.M. Keck Foundation, the Kavli Foundation, the Templeton Foundation and the Burroughs Wellcome Fund.

You can find out more about InnoCentive here. As for other types of artificial eye implants, the latest here is a June 30, 2015 post titled, Clinical trial for bionic eye (artificial retinal implant) shows encouraging results (safety and efficacy).

Chemistry of Cyborgs: review of the state of the art by German researchers

Communication between man and machine – a fascinating area at the interface of chemistry, biomedicine, and engineering. (Figure: KIT/S. Giselbrecht, R. Meyer, B. Rapp)

Communication between man and machine – a fascinating area at the interface of chemistry, biomedicine, and engineering. (Figure: KIT/S. Giselbrecht, R. Meyer, B. Rapp)

German researchers from the Karlsruhe Institute of Technology (KIT), Professor Christof M. Niemeyer and Dr. Stefan Giselbrecht of the Institute for Biological Interfaces 1 (IBG 1) and Dr. Bastian E. Rapp, Institute of Microstructure Technology (IMT) have written a good overview of the current state of cyborgs while pointing out some of the ethical issues associated with this field. From the Jan. 10, 2014 news item on ScienceDaily,

Medical implants, complex interfaces between brain and machine or remotely controlled insects: Recent developments combining machines and organisms have great potentials, but also give rise to major ethical concerns. In a new review, KIT scientists discuss the state of the art of research, opportunities, and risks.

The Jan. ?, 2014 KIT press release (also on EurekAlert with a release date of Jan. 10, 2014), which originated the news item, describes the innovations and the work at KIT in more detail,

They are known from science fiction novels and films – technically modified organisms with extraordinary skills, so-called cyborgs. This name originates from the English term “cybernetic organism”. In fact, cyborgs that combine technical systems with living organisms are already reality. The KIT researchers Professor Christof M. Niemeyer and Dr. Stefan Giselbrecht of the Institute for Biological Interfaces 1 (IBG 1) and Dr. Bastian E. Rapp, Institute of Microstructure Technology (IMT), point out that this especially applies to medical implants.

In recent years, medical implants based on smart materials that automatically react to changing conditions, computer-supported design and fabrication based on magnetic resonance tomography datasets or surface modifications for improved tissue integration allowed major progress to be achieved. For successful tissue integration and the prevention of inflammation reactions, special surface coatings were developed also by the KIT under e.g. the multidisciplinary Helmholtz program “BioInterfaces”.

Progress in microelectronics and semiconductor technology has been the basis of electronic implants controlling, restoring or improving the functions of the human body, such as cardiac pacemakers, retina implants, hearing implants, or implants for deep brain stimulation in pain or Parkinson therapies. Currently, bioelectronic developments are being combined with robotics systems to design highly complex neuroprostheses. Scientists are working on brain-machine interfaces (BMI) for the direct physical contacting of the brain. BMI are used among others to control prostheses and complex movements, such as gripping. Moreover, they are important tools in neurosciences, as they provide insight into the functioning of the brain. Apart from electric signals, substances released by implanted micro- and nanofluidic systems in a spatially or temporarily controlled manner can be used for communication between technical devices and organisms.

BMI are often considered data suppliers. However, they can also be used to feed signals into the brain, which is a highly controversial issue from the ethical point of view. “Implanted BMI that feed signals into nerves, muscles or directly into the brain are already used on a routine basis, e.g. in cardiac pacemakers or implants for deep brain stimulation,” Professor Christof M. Niemeyer, KIT, explains. “But these signals are neither planned to be used nor suited to control the entire organism – brains of most living organisms are far too complex.”

Brains of lower organisms, such as insects, are less complex. As soon as a signal is coupled in, a certain movement program, such as running or flying, is started. So-called biobots, i.e. large insects with implanted electronic and microfluidic control units, are used in a new generation of tools, such as small flying objects for monitoring and rescue missions. In addition, they are applied as model systems in neurosciences in order to understand basic relationships.

Electrically active medical implants that are used for longer terms depend on reliable power supply. Presently, scientists are working on methods to use the patient body’s own thermal, kinetic, electric or chemical energy.

In their review the KIT researchers sum up that developments combining technical devices with organisms have a fascinating potential. They may considerably improve the quality of life of many people in the medical sector in particular. However, ethical and social aspects always have to be taken into account.

After briefly reading the paper, I can say the researchers are most interested in the science and technology aspects but they do have this to say about ethical and social issues in the paper’s conclusion (Note: Links have been removed),

The research and development activities summarized here clearly raise significant social and ethical concerns, in particular, when it comes to the use of BMIs for signal injection into humans, which may lead to modulation or even control of behavior. The ethical issues of this new technology have been discussed in the excellent commentary of Jens Clausen,33 which we highly recommend for further reading. The recently described engineering of a synthetic polymer construct, which is capable of propulsion in water through a collection of adhered rat cardiomyocytes,77 a “medusoid” also described as a “cyborg jellyfish with a rat heart”, brings up an additional ethical aspect. The motivation of the work was to reverse-engineer muscular pumps, and it thus represents fundamental research in tissue engineering for biomedical applications. However, it is also an impressive, early demonstration that autonomous control of technical devices can be achieved through small populations of cells or microtissues. It seems reasonable that future developments along this line will strive, for example, to control complex robots through the use of brain tissue. Given the fact that the robots of today are already capable of autonomously performing complex missions, even in unknown territories,78 this approach might indeed pave the way for yet another entirely new generation of cybernetic organisms.

Here’s a link to and a citation for the English language version of the paper, which is open access (as of Jan. 10, 2014),

The Chemistry of Cyborgs—Interfacing Technical Devices with Organisms by Dr. Stefan Giselbrecht, Dr. Bastian E. Rapp, & Prof.Dr. Christof M. Niemeyer. Angewandte Chemie International Edition Volume 52, Issue 52, pages 13942–13957, December 23, 2013 Article first published online: 29 NOV 2013 DOI: 10.1002/anie.201307495

Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

For those with German language skills,

Chemie der Cyborgs – zur Verknüpfung technischer Systeme mit Lebewesen.  by Stefan Giselbrecht, Bastian E. Rapp, and Christof M. Niemeyer. Angewandte Chemie. Volume 125, issue 52, pages 14190, December 23, 2013. DOI: 10.1002/ange.201307495

I have written many times about cyborgs and neuroprosthetics including this Aug. 30, 2011 posting titled:  Eye, arm, & leg prostheses, cyborgs, eyeborgs, Deus Ex, and ableism, where I mention Gregor Wolbring, a Canadian academic (University of Calgary) who has written extensively on the social and ethical issues of human enhancement technologies. You can find out more on his blog, Nano and Nano- Bio, Info, Cogno, Neuro, Synbio, Geo, Chem…

For anyone wanting to search this blog for these pieces, try using the term machine/flesh as a tag, as well as, human enhancement, neuroprostheses, cyborgs …