Tag Archives: neuroprosthetics

Turning brain-controlled wireless electronic prostheses into reality plus some ethical points

Researchers at Stanford University (California, US) believe they have a solution for a problem with neuroprosthetics (Note: I have included brief comments about neuroprosthetics and possible ethical issues at the end of this posting) according an August 5, 2020 news item on ScienceDaily,

The current generation of neural implants record enormous amounts of neural activity, then transmit these brain signals through wires to a computer. But, so far, when researchers have tried to create wireless brain-computer interfaces to do this, it took so much power to transmit the data that the implants generated too much heat to be safe for the patient. A new study suggests how to solve his problem — and thus cut the wires.

Caption: Photo of a current neural implant, that uses wires to transmit information and receive power. New research suggests how to one day cut the wires. Credit: Sergey Stavisky

An August 3, 2020 Stanford University news release (also on EurekAlert but published August 4, 2020) by Tom Abate, which originated the news item, details the problem and the proposed solution,

Stanford researchers have been working for years to advance a technology that could one day help people with paralysis regain use of their limbs, and enable amputees to use their thoughts to control prostheses and interact with computers.

The team has been focusing on improving a brain-computer interface, a device implanted beneath the skull on the surface of a patient’s brain. This implant connects the human nervous system to an electronic device that might, for instance, help restore some motor control to a person with a spinal cord injury, or someone with a neurological condition like amyotrophic lateral sclerosis, also called Lou Gehrig’s disease.

The current generation of these devices record enormous amounts of neural activity, then transmit these brain signals through wires to a computer. But when researchers have tried to create wireless brain-computer interfaces to do this, it took so much power to transmit the data that the devices would generate too much heat to be safe for the patient.

Now, a team led by electrical engineers and neuroscientists Krishna Shenoy, PhD, and Boris Murmann, PhD, and neurosurgeon and neuroscientist Jaimie Henderson, MD, have shown how it would be possible to create a wireless device, capable of gathering and transmitting accurate neural signals, but using a tenth of the power required by current wire-enabled systems. These wireless devices would look more natural than the wired models and give patients freer range of motion.

Graduate student Nir Even-Chen and postdoctoral fellow Dante Muratore, PhD, describe the team’s approach in a Nature Biomedical Engineering paper.

The team’s neuroscientists identified the specific neural signals needed to control a prosthetic device, such as a robotic arm or a computer cursor. The team’s electrical engineers then designed the circuitry that would enable a future, wireless brain-computer interface to process and transmit these these carefully identified and isolated signals, using less power and thus making it safe to implant the device on the surface of the brain.

To test their idea, the researchers collected neuronal data from three nonhuman primates and one human participant in a (BrainGate) clinical trial.

As the subjects performed movement tasks, such as positioning a cursor on a computer screen, the researchers took measurements. The findings validated their hypothesis that a wireless interface could accurately control an individual’s motion by recording a subset of action-specific brain signals, rather than acting like the wired device and collecting brain signals in bulk.

The next step will be to build an implant based on this new approach and proceed through a series of tests toward the ultimate goal.

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

Power-saving design opportunities for wireless intracortical brain–computer interfaces by Nir Even-Chen, Dante G. Muratore, Sergey D. Stavisky, Leigh R. Hochberg, Jaimie M. Henderson, Boris Murmann & Krishna V. Shenoy. Nature Biomedical Engineering (2020) DOI: https://doi.org/10.1038/s41551-020-0595-9 Published: 03 August 2020

This paper is behind a paywall.

Comments about ethical issues

As I found out while investigating, ethical issues in this area abound. My first thought was to look at how someone with a focus on ability studies might view the complexities.

My ‘go to’ resource for human enhancement and ethical issues is Gregor Wolbring, an associate professor at the University of Calgary (Alberta, Canada). his profile lists these areas of interest: ability studies, disability studies, governance of emerging and existing sciences and technologies (e.g. neuromorphic engineering, genetics, synthetic biology, robotics, artificial intelligence, automatization, brain machine interfaces, sensors) and more.

I can’t find anything more recent on this particular topic but I did find an August 10, 2017 essay for The Conversation where he comments on technology and human enhancement ethical issues where the technology is gene-editing. Regardless, he makes points that are applicable to brain-computer interfaces (human enhancement), Note: Links have been removed),

Ability expectations have been and still are used to disable, or disempower, many people, not only people seen as impaired. They’ve been used to disable or marginalize women (men making the argument that rationality is an important ability and women don’t have it). They also have been used to disable and disempower certain ethnic groups (one ethnic group argues they’re smarter than another ethnic group) and others.

A recent Pew Research survey on human enhancement revealed that an increase in the ability to be productive at work was seen as a positive. What does such ability expectation mean for the “us” in an era of scientific advancements in gene-editing, human enhancement and robotics?

Which abilities are seen as more important than others?

The ability expectations among “us” will determine how gene-editing and other scientific advances will be used.

And so how we govern ability expectations, and who influences that governance, will shape the future. Therefore, it’s essential that ability governance and ability literacy play a major role in shaping all advancements in science and technology.

One of the reasons I find Gregor’s commentary so valuable is that he writes lucidly about ability and disability as concepts and poses what can be provocative questions about expectations and what it is to be truly abled or disabled. You can find more of his writing here on his eponymous (more or less) blog.

Ethics of clinical trials for testing brain implants

This October 31, 2017 article by Emily Underwood for Science was revelatory,

In 2003, neurologist Helen Mayberg of Emory University in Atlanta began to test a bold, experimental treatment for people with severe depression, which involved implanting metal electrodes deep in the brain in a region called area 25 [emphases mine]. The initial data were promising; eventually, they convinced a device company, St. Jude Medical in Saint Paul, to sponsor a 200-person clinical trial dubbed BROADEN.

This month [October 2017], however, Lancet Psychiatry reported the first published data on the trial’s failure. The study stopped recruiting participants in 2012, after a 6-month study in 90 people failed to show statistically significant improvements between those receiving active stimulation and a control group, in which the device was implanted but switched off.

… a tricky dilemma for companies and research teams involved in deep brain stimulation (DBS) research: If trial participants want to keep their implants [emphases mine], who will take responsibility—and pay—for their ongoing care? And participants in last week’s meeting said it underscores the need for the growing corps of DBS researchers to think long-term about their planned studies.

… participants bear financial responsibility for maintaining the device should they choose to keep it, and for any additional surgeries that might be needed in the future, Mayberg says. “The big issue becomes cost [emphasis mine],” she says. “We transition from having grants and device donations” covering costs, to patients being responsible. And although the participants agreed to those conditions before enrolling in the trial, Mayberg says she considers it a “moral responsibility” to advocate for lower costs for her patients, even it if means “begging for charity payments” from hospitals. And she worries about what will happen to trial participants if she is no longer around to advocate for them. “What happens if I retire, or get hit by a bus?” she asks.

There’s another uncomfortable possibility: that the hypothesis was wrong [emphases mine] to begin with. A large body of evidence from many different labs supports the idea that area 25 is “key to successful antidepressant response,” Mayberg says. But “it may be too simple-minded” to think that zapping a single brain node and its connections can effectively treat a disease as complex as depression, Krakauer [John Krakauer, a neuroscientist at Johns Hopkins University in Baltimore, Maryland] says. Figuring that out will likely require more preclinical research in people—a daunting prospect that raises additional ethical dilemmas, Krakauer says. “The hardest thing about being a clinical researcher,” he says, “is knowing when to jump.”

Brain-computer interfaces, symbiosis, and ethical issues

This was the most recent and most directly applicable work that I could find. From a July 24, 2019 article by Liam Drew for Nature Outlook: The brain,

“It becomes part of you,” Patient 6 said, describing the technology that enabled her, after 45 years of severe epilepsy, to halt her disabling seizures. Electrodes had been implanted on the surface of her brain that would send a signal to a hand-held device when they detected signs of impending epileptic activity. On hearing a warning from the device, Patient 6 knew to take a dose of medication to halt the coming seizure.

“You grow gradually into it and get used to it, so it then becomes a part of every day,” she told Frederic Gilbert, an ethicist who studies brain–computer interfaces (BCIs) at the University of Tasmania in Hobart, Australia. “It became me,” she said. [emphasis mine]

Gilbert was interviewing six people who had participated in the first clinical trial of a predictive BCI to help understand how living with a computer that monitors brain activity directly affects individuals psychologically1. Patient 6’s experience was extreme: Gilbert describes her relationship with her BCI as a “radical symbiosis”.

Symbiosis is a term, borrowed from ecology, that means an intimate co-existence of two species for mutual advantage. As technologists work towards directly connecting the human brain to computers, it is increasingly being used to describe humans’ potential relationship with artificial intelligence.

Interface technologies are divided into those that ‘read’ the brain to record brain activity and decode its meaning, and those that ‘write’ to the brain to manipulate activity in specific regions and affect their function.

Commercial research is opaque, but scientists at social-media platform Facebook are known to be pursuing brain-reading techniques for use in headsets that would convert users’ brain activity into text. And neurotechnology companies such as Kernel in Los Angeles, California, and Neuralink, founded by Elon Musk in San Francisco, California, predict bidirectional coupling in which computers respond to people’s brain activity and insert information into their neural circuitry. [emphasis mine]

Already, it is clear that melding digital technologies with human brains can have provocative effects, not least on people’s agency — their ability to act freely and according to their own choices. Although neuroethicists’ priority is to optimize medical practice, their observations also shape the debate about the development of commercial neurotechnologies.

Neuroethicists began to note the complex nature of the therapy’s side effects. “Some effects that might be described as personality changes are more problematic than others,” says Maslen [Hannah Maslen, a neuroethicist at the University of Oxford, UK]. A crucial question is whether the person who is undergoing stimulation can reflect on how they have changed. Gilbert, for instance, describes a DBS patient who started to gamble compulsively, blowing his family’s savings and seeming not to care. He could only understand how problematic his behaviour was when the stimulation was turned off.

Such cases present serious questions about how the technology might affect a person’s ability to give consent to be treated, or for treatment to continue. [emphases mine] If the person who is undergoing DBS is happy to continue, should a concerned family member or doctor be able to overrule them? If someone other than the patient can terminate treatment against the patient’s wishes, it implies that the technology degrades people’s ability to make decisions for themselves. It suggests that if a person thinks in a certain way only when an electrical current alters their brain activity, then those thoughts do not reflect an authentic self.

To observe a person with tetraplegia bringing a drink to their mouth using a BCI-controlled robotic arm is spectacular. [emphasis mine] This rapidly advancing technology works by implanting an array of electrodes either on or in a person’s motor cortex — a brain region involved in planning and executing movements. The activity of the brain is recorded while the individual engages in cognitive tasks, such as imagining that they are moving their hand, and these recordings are used to command the robotic limb.

If neuroscientists could unambiguously discern a person’s intentions from the chattering electrical activity that they record in the brain, and then see that it matched the robotic arm’s actions, ethical concerns would be minimized. But this is not the case. The neural correlates of psychological phenomena are inexact and poorly understood, which means that signals from the brain are increasingly being processed by artificial intelligence (AI) software before reaching prostheses.[emphasis mine]

But, he [Philipp Kellmeyer, a neurologist and neuroethicist at the University of Freiburg, Germany] says, using AI tools also introduces ethical issues of which regulators have little experience. [emphasis mine] Machine-learning software learns to analyse data by generating algorithms that cannot be predicted and that are difficult, or impossible, to comprehend. This introduces an unknown and perhaps unaccountable process between a person’s thoughts and the technology that is acting on their behalf.

Maslen is already helping to shape BCI-device regulation. She is in discussion with the European Commission about regulations it will implement in 2020 that cover non-invasive brain-modulating devices that are sold straight to consumers. [emphases mine; Note: There is a Canadian company selling this type of product, MUSE] Maslen became interested in the safety of these devices, which were covered by only cursory safety regulations. Although such devices are simple, they pass electrical currents through people’s scalps to modulate brain activity. Maslen found reports of them causing burns, headaches and visual disturbances. She also says clinical studies have shown that, although non-invasive electrical stimulation of the brain can enhance certain cognitive abilities, this can come at the cost of deficits in other aspects of cognition.

Regarding my note about MUSE, the company is InteraXon and its product is MUSE.They advertise the product as “Brain Sensing Headbands That Improve Your Meditation Practice.” The company website and the product seem to be one entity, Choose Muse. The company’s product has been used in some serious research papers they can be found here. I did not see any research papers concerning safety issues.

Getting back to Drew’s July 24, 2019 article and Patient 6,

… He [Gilbert] is now preparing a follow-up report on Patient 6. The company that implanted the device in her brain to help free her from seizures went bankrupt. The device had to be removed.

… Patient 6 cried as she told Gilbert about losing the device. … “I lost myself,” she said.

“It was more than a device,” Gilbert says. “The company owned the existence of this new person.”

I strongly recommend reading Drew’s July 24, 2019 article in its entirety.

Finally

It’s easy to forget that in all the excitement over technologies ‘making our lives better’ that there can be a dark side or two. Some of the points brought forth in the articles by Wolbring, Underwood, and Drew confirmed my uneasiness as reasonable and gave me some specific examples of how these technologies raise new issues or old issues in new ways.

What I find interesting is that no one is using the term ‘cyborg’, which would seem quite applicable.There is an April 20, 2012 posting here titled ‘My mother is a cyborg‘ where I noted that by at lease one definition people with joint replacements, pacemakers, etc. are considered cyborgs. In short, cyborgs or technology integrated into bodies have been amongst us for quite some time.

Interestingly, no one seems to care much when insects are turned into cyborgs (can’t remember who pointed this out) but it is a popular area of research especially for military applications and search and rescue applications.

I’ve sometimes used the term ‘machine/flesh’ and or ‘augmentation’ as a description of technologies integrated with bodies, human or otherwise. You can find lots on the topic here however I’ve tagged or categorized it.

Amongst other pieces you can find here, there’s the August 8, 2016 posting, ‘Technology, athletics, and the ‘new’ human‘ featuring Oscar Pistorius when he was still best known as the ‘blade runner’ and a remarkably successful paralympic athlete. It’s about his efforts to compete against able-bodied athletes at the London Olympic Games in 2012. It is fascinating to read about technology and elite athletes of any kind as they are often the first to try out ‘enhancements’.

Gregor Wolbring has a number of essays on The Conversation looking at Paralympic athletes and their pursuit of enhancements and how all of this is affecting our notions of abilities and disabilities. By extension, one has to assume that ‘abled’ athletes are also affected with the trickle-down effect on the rest of us.

Regardless of where we start the investigation, there is a sameness to the participants in neuroethics discussions with a few experts and commercial interests deciding on how the rest of us (however you define ‘us’ as per Gregor Wolbring’s essay) will live.

This paucity of perspectives is something I was getting at in my COVID-19 editorial for the Canadian Science Policy Centre. My thesis being that we need a range of ideas and insights that cannot be culled from small groups of people who’ve trained and read the same materials or entrepreneurs who too often seem to put profit over thoughtful implementations of new technologies. (See the PDF May 2020 edition [you’ll find me under Policy Development]) or see my May 15, 2020 posting here (with all the sources listed.)

As for this new research at Stanford, it’s exciting news, which raises questions, as it offers the hope of independent movement for people diagnosed as tetraplegic (sometimes known as quadriplegic.)

Living with a mind-controlled prosthetic

This could be described as the second half of an October 10, 2014 post (Mind-controlled prostheses ready for real world activities). Five and a half years later, Sweden’s Chalmers University of Technology has announced mind-controlled prosthetics in daily use that feature the sense of touch. From an April 30, 2020 Chalmers University of Technology press release (also on EurekAlert but published April 29, 2020) by Johanna Wilde,

For the first time, people with arm amputations can experience sensations of touch in a mind-controlled arm prosthesis that they use in everyday life. A study in the New England Journal of Medicine reports on three Swedish patients who have lived, for several years, with this new technology – one of the world’s most integrated interfaces between human and machine.

See the film: “The most natural robotic prosthesis in the world” [Should you not have Swedish language skills, you can click on the subtitle option in the video’s settings field]

The advance is unique: the patients have used a mind-controlled prosthesis in their everyday life for up to seven years. For the last few years, they have also lived with a new function – sensations of touch in the prosthetic hand. This is a new concept for artificial limbs, which are called neuromusculoskeletal prostheses – as they are connected to the user’s nerves, muscles, and skeleton.

The research was led by Max Ortiz Catalan, Associate Professor at Chalmers University of Technology, in collaboration with Sahlgrenska University Hospital, University of Gothenburg, and Integrum AB, all in Gothenburg, Sweden. Researchers at Medical University of Vienna in Austria and the Massachusetts Institute of Technology in the USA were also involved.

“Our study shows that a prosthetic hand, attached to the bone and controlled by electrodes implanted in nerves and muscles, can operate much more precisely than conventional prosthetic hands. We further improved the use of the prosthesis by integrating tactile sensory feedback that the patients use to mediate how hard to grab or squeeze an object. Over time, the ability of the patients to discern smaller changes in the intensity of sensations has improved,” says Max Ortiz Catalan.

“The most important contribution of this study was to demonstrate that this new type of prosthesis is a clinically viable replacement for a lost arm. No matter how sophisticated a neural interface becomes, it can only deliver real benefit to patients if the connection between the patient and the prosthesis is safe and reliable in the long term. Our results are the product of many years of work, and now we can finally present the first bionic arm prosthesis that can be reliably controlled using implanted electrodes, while also conveying sensations to the user in everyday life”, continues Max Ortiz Catalan.

Since receiving their prostheses, the patients have used them daily in all their professional and personal activities.

The new concept of a neuromusculoskeletal prosthesis is unique in that it delivers several different features which have not been presented together in any other prosthetic technology in the world:

[1] It has a direct connection to a person’s nerves, muscles, and skeleton.

[2] It is mind-controlled and delivers sensations that are perceived by the user as arising from the missing hand.

[3] It is self-contained; all electronics needed are contained within the prosthesis, so patients do not need to carry additional equipment or batteries.

[4] It is safe and stable in the long term; the technology has been used without interruption by patients during their everyday activities, without supervision from the researchers, and it is not restricted to confined or controlled environments.

The newest part of the technology, the sensation of touch, is possible through stimulation of the nerves that used to be connected to the biological hand before the amputation. Force sensors located in the thumb of the prosthesis measure contact and pressure applied to an object while grasping. This information is transmitted to the patients’ nerves leading to their brains. Patients can thus feel when they are touching an object, its characteristics, and how hard they are pressing it, which is crucial for imitating a biological hand.

“Currently, the sensors are not the obstacle for restoring sensation,” says Max Ortiz Catalan. “The challenge is creating neural interfaces that can seamlessly transmit large amounts of artificially collected information to the nervous system, in a way that the user can experience sensations naturally and effortlessly.”
The implantation of this new technology took place at Sahlgrenska University Hospital, led by Professor Rickard Brånemark and Doctor Paolo Sassu. Over a million people worldwide suffer from limb loss, and the end goal for the research team, in collaboration with Integrum AB, is to develop a widely available product suitable for as many of these people as possible.

“Right now, patients in Sweden are participating in the clinical validation of this new prosthetic technology for arm amputation,” says Max Ortiz Catalan. “We expect this system to become available outside Sweden within a couple of years, and we are also making considerable progress with a similar technology for leg prostheses, which we plan to implant in a first patient later this year.”

More about: How the technology works:

The implant system for the arm prosthesis is called e-OPRA and is based on the OPRA implant system created by Integrum AB. The implant system anchors the prosthesis to the skeleton in the stump of the amputated limb, through a process called osseointegration (osseo = bone). Electrodes are implanted in muscles and nerves inside the amputation stump, and the e-OPRA system sends signals in both directions between the prosthesis and the brain, just like in a biological arm.

The prosthesis is mind-controlled, via the electrical muscle and nerve signals sent through the arm stump and captured by the electrodes. The signals are passed into the implant, which goes through the skin and connects to the prosthesis. The signals are then interpreted by an embedded control system developed by the researchers. The control system is small enough to fit inside the prosthesis and it processes the signals using sophisticated artificial intelligence algorithms, resulting in control signals for the prosthetic hand’s movements.

The touch sensations arise from force sensors in the prosthetic thumb. The signals from the sensors are converted by the control system in the prosthesis into electrical signals which are sent to stimulate a nerve in the arm stump. The nerve leads to the brain, which then perceives the pressure levels against the hand.

The neuromusculoskeletal implant can connect to any commercially available arm prosthesis, allowing them to operate more effectively.

More about: How the artificial sensation is experienced:

People who lose an arm or leg often experience phantom sensations, as if the missing body part remains although not physically present. When the force sensors in the prosthetic thumb react, the patients in the study feel that the sensation comes from their phantom hand. Precisely where on the phantom hand varies between patients, depending on which nerves in the stump receive the signals. The lowest level of pressure can be compared to touching the skin with the tip of a pencil. As the pressure increases, the feeling becomes stronger and increasingly ‘electric’.

I have read elsewhere that one of the most difficult aspects of dealing with a prosthetic is the loss of touch. This has to be exciting news for a lot of people. Here’s a link to and a citation for the paper,

Self-Contained Neuromusculoskeletal Arm Prostheses by Max Ortiz-Catalan, Enzo Mastinu, Paolo Sassu, Oskar Aszmann, and Rickard Brånemark. N Engl J Med 2020; 382:1732-1738 DOI: 10.1056/NEJMoa1917537 Published: April 30, 2020

This paper is behind a paywall.

Two approaches to memristors

Within one day of each other in October 2018, two different teams working on memristors with applications to neuroprosthetics and neuromorphic computing (brainlike computing) announced their results.

Russian team

An October 15, 2018 (?) Lobachevsky University press release (also published on October 15, 2018 on EurekAlert) describes a new approach to memristors,

Biological neurons are coupled unidirectionally through a special junction called a synapse. An electrical signal is transmitted along a neuron after some biochemical reactions initiate a chemical release to activate an adjacent neuron. These junctions are crucial for cognitive functions, such as perception, learning and memory.

A group of researchers from Lobachevsky University in Nizhny Novgorod investigates the dynamics of an individual memristive device when it receives a neuron-like signal as well as the dynamics of a network of analog electronic neurons connected by means of a memristive device. According to Svetlana Gerasimova, junior researcher at the Physics and Technology Research Institute and at the Neurotechnology Department of Lobachevsky University, this system simulates the interaction between synaptically coupled brain neurons while the memristive device imitates a neuron axon.

A memristive device is a physical model of Chua’s [Dr. Leon Chua, University of California at Berkeley; see my May 9, 2008 posting for a brief description Dr. Chua’s theory] memristor, which is an electric circuit element capable of changing its resistance depending on the electric signal received at the input. The device based on a Au/ZrO2(Y)/TiN/Ti structure demonstrates reproducible bipolar switching between the low and high resistance states. Resistive switching is determined by the oxidation and reduction of segments of conducting channels (filaments) in the oxide film when voltage with different polarity is applied to it. In the context of the present work, the ability of a memristive device to change conductivity under the action of pulsed signals makes it an almost ideal electronic analog of a synapse.

Lobachevsky University scientists and engineers supported by the Russian Science Foundation (project No.16-19-00144) have experimentally implemented and theoretically described the synaptic connection of neuron-like generators using the memristive interface and investigated the characteristics of this connection.

“Each neuron is implemented in the form of a pulse signal generator based on the FitzHugh-Nagumo model. This model provides a qualitative description of the main neurons’ characteristics: the presence of the excitation threshold, the presence of excitable and self-oscillatory regimes with the possibility of a changeover. At the initial time moment, the master generator is in the self-oscillatory mode, the slave generator is in the excitable mode, and the memristive device is used as a synapse. The signal from the master generator is conveyed to the input of the memristive device, the signal from the output of the memristive device is transmitted to the input of the slave generator via the loading resistance. When the memristive device switches from a high resistance to a low resistance state, the connection between the two neuron-like generators is established. The master generator goes into the oscillatory mode and the signals of the generators are synchronized. Different signal modulation mode synchronizations were demonstrated for the Au/ZrO2(Y)/TiN/Ti memristive device,” – says Svetlana Gerasimova.

UNN researchers believe that the next important stage in the development of neuromorphic systems based on memristive devices is to apply such systems in neuroprosthetics. Memristive systems will provide a highly efficient imitation of synaptic connection due to the stochastic nature of the memristive phenomenon and can be used to increase the flexibility of the connections for neuroprosthetic purposes. Lobachevsky University scientists have vast experience in the development of neurohybrid systems. In particular, a series of experiments was performed with the aim of connecting the FitzHugh-Nagumo oscillator with a biological object, a rat brain hippocampal slice. The signal from the electronic neuron generator was transmitted through the optic fiber communication channel to the bipolar electrode which stimulated Schaffer collaterals (axons of pyramidal neurons in the CA3 field) in the hippocampal slices. “We are going to combine our efforts in the design of artificial neuromorphic systems and our experience of working with living cells to improve flexibility of prosthetics,” concludes S. Gerasimova.

The results of this research were presented at the 38th International Conference on Nonlinear Dynamics (Dynamics Days Europe) at Loughborough University (Great Britain).

This diagram illustrates an aspect of the work,

Caption: Schematic of electronic neurons coupling via a memristive device. Credit: Lobachevsky University

US team

The American Institute of Physics (AIP) announced the publication of a ‘memristor paper’ by a team from the University of Southern California (USC) in an October 16, 2018 news item on phys.org,

Just like their biological counterparts, hardware that mimics the neural circuitry of the brain requires building blocks that can adjust how they synapse, with some connections strengthening at the expense of others. One such approach, called memristors, uses current resistance to store this information. New work looks to overcome reliability issues in these devices by scaling memristors to the atomic level.

An October 16, 2018 AIP news release (also on EurekAlert), which originated the news item, delves further into the particulars of this particular piece of memristor research,

A group of researchers demonstrated a new type of compound synapse that can achieve synaptic weight programming and conduct vector-matrix multiplication with significant advances over the current state of the art. Publishing its work in the Journal of Applied Physics, from AIP Publishing, the group’s compound synapse is constructed with atomically thin boron nitride memristors running in parallel to ensure efficiency and accuracy.

The article appears in a special topic section of the journal devoted to “New Physics and Materials for Neuromorphic Computation,” which highlights new developments in physical and materials science research that hold promise for developing the very large-scale, integrated “neuromorphic” systems of tomorrow that will carry computation beyond the limitations of current semiconductors today.

“There’s a lot of interest in using new types of materials for memristors,” said Ivan Sanchez Esqueda, an author on the paper. “What we’re showing is that filamentary devices can work well for neuromorphic computing applications, when constructed in new clever ways.”

Current memristor technology suffers from a wide variation in how signals are stored and read across devices, both for different types of memristors as well as different runs of the same memristor. To overcome this, the researchers ran several memristors in parallel. The combined output can achieve accuracies up to five times those of conventional devices, an advantage that compounds as devices become more complex.

The choice to go to the subnanometer level, Sanchez said, was born out of an interest to keep all of these parallel memristors energy-efficient. An array of the group’s memristors were found to be 10,000 times more energy-efficient than memristors currently available.

“It turns out if you start to increase the number of devices in parallel, you can see large benefits in accuracy while still conserving power,” Sanchez said. Sanchez said the team next looks to further showcase the potential of the compound synapses by demonstrating their use completing increasingly complex tasks, such as image and pattern recognition.

Here’s an image illustrating the parallel artificial synapses,

Caption: Hardware that mimics the neural circuitry of the brain requires building blocks that can adjust how they synapse. One such approach, called memristors, uses current resistance to store this information. New work looks to overcome reliability issues in these devices by scaling memristors to the atomic level. Researchers demonstrated a new type of compound synapse that can achieve synaptic weight programming and conduct vector-matrix multiplication with significant advances over the current state of the art. They discuss their work in this week’s Journal of Applied Physics. This image shows a conceptual schematic of the 3D implementation of compound synapses constructed with boron nitride oxide (BNOx) binary memristors, and the crossbar array with compound BNOx synapses for neuromorphic computing applications. Credit: Ivan Sanchez Esqueda

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

Efficient learning and crossbar operations with atomically-thin 2-D material compound synapses by Ivan Sanchez Esqueda, Huan Zhao and Han Wang. The article will appear in the Journal of Applied Physics Oct. 16, 2018 (DOI: 10.1063/1.5042468).

This paper is behind a paywall.

*Title corrected from ‘Two approaches to memristors featuring’ to ‘Two approaches to memristors’ on May 31, 2019 at 1455 hours PDT.

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.

Singapore’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!

*’Sinagpore’ in head changed to ‘Singapore’ on May 14, 2019.

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.