Tag Archives: neuroprosthetics

Unveiling the Neurotechnology Landscape: Scientific Advancements, Innovations and Major Trends—a UNESCO report

Launched on Thursday, July 13, 2023 during UNESCO’s (United Nations Educational, Scientific, and Cultural Organization) “Global dialogue on the ethics of neurotechnology,” is a report tying together the usual measures of national scientific supremacy (number of papers published and number of patents filed) with information on corporate investment in the field. Consequently, “Unveiling the Neurotechnology Landscape: Scientific Advancements, Innovations and Major Trends” by Daniel S. Hain, Roman Jurowetzki, Mariagrazia Squicciarini, and Lihui Xu provides better insight into the international neurotechnology scene than is sometimes found in these kinds of reports. By the way, the report is open access.

Here’s what I mean, from the report‘s short summary,

Since 2013, government investments in this field have exceeded $6 billion. Private investment has also seen significant growth, with annual funding experiencing a 22-fold increase from 2010 to 2020, reaching $7.3 billion and totaling $33.2 billion.

This investment has translated into a 35-fold growth in neuroscience publications between 2000-2021 and 20-fold growth in innovations between 2022-2020, as proxied by patents. However, not all are poised to benefit from such developments, as big divides emerge.

Over 80% of high-impact neuroscience publications are produced by only ten countries, while 70% of countries contributed fewer than 10 such papers over the period considered. Similarly, five countries only hold 87% of IP5 neurotech patents.

This report sheds light on the neurotechnology ecosystem, that is, what is being developed, where and by whom, and informs about how neurotechnology interacts with other technological trajectories, especially Artificial Intelligence [emphasis mine]. [p. 2]

The money aspect is eye-opening even when you already have your suspicions. Also, it’s not entirely unexpected to learn that only ten countries produce over 80% of the high impact neurotech papers and that only five countries hold 87% of the IP5 neurotech patents but it is stunning to see it in context. (If you’re not familiar with the term ‘IP5 patents’, scroll down in this post to the relevant subhead. Hint: It means the patent was filed in one of the top five jurisdictions; I’ll leave you to guess which ones those might be.)

“Since 2013 …” isn’t quite as informative as the authors may have hoped. I wish they had given a time frame for government investments similar to what they did for corporate investments (e.g., 2010 – 2020). Also, is the $6B (likely in USD) government investment cumulative or an estimated annual number? To sum up, I would have appreciated parallel structure and specificity.

Nitpicks aside, there’s some very good material intended for policy makers. On that note, some of the analysis is beyond me. I haven’t used anything even somewhat close to their analytical tools in years and years. This commentaries reflects my interests and a very rapid reading. One last thing, this is being written from a Canadian perspective. With those caveats in mind, here’s some of what I found.

A definition, social issues, country statistics, and more

There’s a definition for neurotechnology and a second mention of artificial intelligence being used in concert with neurotechnology. From the report‘s executive summary,

Neurotechnology consists of devices and procedures used to access, monitor, investigate, assess, manipulate, and/or emulate the structure and function of the neural systems of animals or human beings. It is poised to revolutionize our understanding of the brain and to unlock innovative solutions to treat a wide range of diseases and disorders.

Similarly to Artificial Intelligence (AI), and also due to its convergence with AI, neurotechnology may have profound societal and economic impact, beyond the medical realm. As neurotechnology directly relates to the brain, it triggers ethical considerations about fundamental aspects of human existence, including mental integrity, human dignity, personal identity, freedom of thought, autonomy, and privacy [emphases mine]. Its potential for enhancement purposes and its accessibility further amplifies its prospect social and societal implications.

The recent discussions held at UNESCO’s Executive Board further shows Member States’ desire to address the ethics and governance of neurotechnology through the elaboration of a new standard-setting instrument on the ethics of neurotechnology, to be adopted in 2025. To this end, it is important to explore the neurotechnology landscape, delineate its boundaries, key players, and trends, and shed light on neurotech’s scientific and technological developments. [p. 7]

Here’s how they sourced the data for the report,

The present report addresses such a need for evidence in support of policy making in
relation to neurotechnology by devising and implementing a novel methodology on data from scientific articles and patents:

● We detect topics over time and extract relevant keywords using a transformer-
based language models fine-tuned for scientific text. Publication data for the period
2000-2021 are sourced from the Scopus database and encompass journal articles
and conference proceedings in English. The 2,000 most cited publications per year
are further used in in-depth content analysis.
● Keywords are identified through Named Entity Recognition and used to generate
search queries for conducting a semantic search on patents’ titles and abstracts,
using another language model developed for patent text. This allows us to identify
patents associated with the identified neuroscience publications and their topics.
The patent data used in the present analysis are sourced from the European
Patent Office’s Worldwide Patent Statistical Database (PATSTAT). We consider
IP5 patents filed between 2000-2020 having an English language abstract and
exclude patents solely related to pharmaceuticals.

This approach allows mapping the advancements detailed in scientific literature to the technological applications contained in patent applications, allowing for an analysis of the linkages between science and technology. This almost fully automated novel approach allows repeating the analysis as neurotechnology evolves. [pp. 8-9[

Findings in bullet points,

Key stylized facts are:
● The field of neuroscience has witnessed a remarkable surge in the overall number
of publications since 2000, exhibiting a nearly 35-fold increase over the period
considered, reaching 1.2 million in 2021. The annual number of publications in
neuroscience has nearly tripled since 2000, exceeding 90,000 publications a year
in 2021. This increase became even more pronounced since 2019.
● The United States leads in terms of neuroscience publication output (40%),
followed by the United Kingdom (9%), Germany (7%), China (5%), Canada (4%),
Japan (4%), Italy (4%), France (4%), the Netherlands (3%), and Australia (3%).
These countries account for over 80% of neuroscience publications from 2000 to
2021.
● Big divides emerge, with 70% of countries in the world having less than 10 high-
impact neuroscience publications between 2000 to 2021.
● Specific neurotechnology-related research trends between 2000 and 2021 include:
○ An increase in Brain-Computer Interface (BCI) research around 2010,
maintaining a consistent presence ever since.
○ A significant surge in Epilepsy Detection research in 2017 and 2018,
reflecting the increased use of AI and machine learning in healthcare.
○ Consistent interest in Neuroimaging Analysis, which peaks around 2004,
likely because of its importance in brain activity and language
comprehension studies.
○ While peaking in 2016 and 2017, Deep Brain Stimulation (DBS) remains a
persistent area of research, underlining its potential in treating conditions
like Parkinson’s disease and essential tremor.
● Between 2000 and 2020, the total number of patent applications in this field
increased significantly, experiencing a 20-fold increase from less than 500 to over
12,000. In terms of annual figures, a consistent upward trend in neurotechnology-10
related patent applications emerges, with a notable doubling observed between
2015 and 2020.
• The United States account for nearly half of all worldwide patent applications (47%).
Other major contributors include South Korea (11%), China (10%), Japan (7%),
Germany (7%), and France (5%). These five countries together account for 87%
of IP5 neurotech patents applied between 2000 and 2020.
○ The United States has historically led the field, with a peak around 2010, a
decline towards 2015, and a recovery up to 2020.
○ South Korea emerged as a significant contributor after 1990, overtaking
Germany in the late 2000s to become the second-largest developer of
neurotechnology. By the late 2010s, South Korea’s annual neurotechnology
patent applications approximated those of the United States.
○ China exhibits a sharp increase in neurotechnology patent applications in
the mid-2010s, bringing it on par with the United States in terms of
application numbers.
● The United States ranks highest in both scientific publications and patents,
indicating their strong ability to transform knowledge into marketable inventions.
China, France, and Korea excel in leveraging knowledge to develop patented
innovations. Conversely, countries such as the United Kingdom, Germany, Italy,
Canada, Brazil, and Australia lag behind in effectively translating neurotech
knowledge into patentable innovations.
● In terms of patent quality measured by forward citations, the leading countries are
Germany, US, China, Japan, and Korea.
● A breakdown of patents by technology field reveals that Computer Technology is
the most important field in neurotechnology, exceeding Medical Technology,
Biotechnology, and Pharmaceuticals. The growing importance of algorithmic
applications, including neural computing techniques, also emerges by looking at
the increase in patent applications in these fields between 2015-2020. Compared
to the reference year, computer technologies-related patents in neurotech
increased by 355% and by 92% in medical technology.
● An analysis of the specialization patterns of the top-5 countries developing
neurotechnologies reveals that Germany has been specializing in chemistry-
related technology fields, whereas Asian countries, particularly South Korea and
China, focus on computer science and electrical engineering-related fields. The
United States exhibits a balanced configuration with specializations in both
chemistry and computer science-related fields.
● The entities – i.e. both companies and other institutions – leading worldwide
innovation in the neurotech space are: IBM (126 IP5 patents, US), Ping An
Technology (105 IP5 patents, CH), Fujitsu (78 IP5 patents, JP), Microsoft (76 IP511
patents, US)1, Samsung (72 IP5 patents, KR), Sony (69 IP5 patents JP) and Intel
(64 IP5 patents US)

This report further proposes a pioneering taxonomy of neurotechnologies based on International Patent Classification (IPC) codes.

• 67 distinct patent clusters in neurotechnology are identified, which mirror the diverse research and development landscape of the field. The 20 most prominent neurotechnology groups, particularly in areas like multimodal neuromodulation, seizure prediction, neuromorphic computing [emphasis mine], and brain-computer interfaces, point to potential strategic areas for research and commercialization.
• The variety of patent clusters identified mirrors the breadth of neurotechnology’s potential applications, from medical imaging and limb rehabilitation to sleep optimization and assistive exoskeletons.
• The development of a baseline IPC-based taxonomy for neurotechnology offers a structured framework that enriches our understanding of this technological space, and can facilitate research, development and analysis. The identified key groups mirror the interdisciplinary nature of neurotechnology and underscores the potential impact of neurotechnology, not only in healthcare but also in areas like information technology and biomaterials, with non-negligible effects over societies and economies.

1 If we consider Microsoft Technology Licensing LLM and Microsoft Corporation as being under the same umbrella, Microsoft leads worldwide developments with 127 IP5 patents. Similarly, if we were to consider that Siemens AG and Siemens Healthcare GmbH belong to the same conglomerate, Siemens would appear much higher in the ranking, in third position, with 84 IP5 patents. The distribution of intellectual property assets across companies belonging to the same conglomerate is frequent and mirrors strategic as well as operational needs and features, among others. [pp. 9-11]

Surprises and comments

Interesting and helpful to learn that “neurotechnology interacts with other technological trajectories, especially Artificial Intelligence;” this has changed and improved my understanding of neurotechnology.

It was unexpected to find Canada in the top ten countries producing neuroscience papers. However, finding out that the country lags in translating its ‘neuro’ knowledge into patentable innovation is not entirely a surprise.

It can’t be an accident that countries with major ‘electronics and computing’ companies lead in patents. These companies do have researchers but they also buy startups to acquire patents. They (and ‘patent trolls’) will also file patents preemptively. For the patent trolls, it’s a moneymaking proposition and for the large companies, it’s a way of protecting their own interests and/or (I imagine) forcing a sale.

The mention of neuromorphic (brainlike) computing in the taxonomy section was surprising and puzzling. Up to this point, I’ve thought of neuromorphic computing as a kind of alternative or addition to standard computing but the authors have blurred the lines as per UNESCO’s definition of neurotechnology (specifically, “… emulate the structure and function of the neural systems of animals or human beings”) . Again, this report is broadening my understanding of neurotechnology. Of course, it required two instances before I quite grasped it, the definition and the taxonomy.

What’s puzzling is that neuromorphic engineering, a broader term that includes neuromorphic computing, isn’t used or mentioned. (For an explanation of the terms neuromorphic computing and neuromorphic engineering, there’s my June 23, 2023 posting, “Neuromorphic engineering: an overview.” )

The report

I won’t have time for everything. Here are some of the highlights from my admittedly personal perspective.

It’s not only about curing disease

From the report,

Neurotechnology’s applications however extend well beyond medicine [emphasis mine], and span from research, to education, to the workplace, and even people’s everyday life. Neurotechnology-based solutions may enhance learning and skill acquisition and boost focus through brain stimulation techniques. For instance, early research finds that brain- zapping caps appear to boost memory for at least one month (Berkeley, 2022). This could one day be used at home to enhance memory functions [emphasis mine]. They can further enable new ways to interact with the many digital devices we use in everyday life, transforming the way we work, live and interact. One example is the Sound Awareness wristband developed by a Stanford team (Neosensory, 2022) which enables individuals to “hear” by converting sound into tactile feedback, so that sound impaired individuals can perceive spoken words through their skin. Takagi and Nishimoto (2023) analyzed the brain scans taken through Magnetic Resonance Imaging (MRI) as individuals were shown thousands of images. They then trained a generative AI tool called Stable Diffusion2 on the brain scan data of the study’s participants, thus creating images that roughly corresponded to the real images shown. While this does not correspond to reading the mind of people, at least not yet, and some limitations of the study have been highlighted (Parshall, 2023), it nevertheless represents an important step towards developing the capability to interface human thoughts with computers [emphasis mine], via brain data interpretation.

While the above examples may sound somewhat like science fiction, the recent uptake of generative Artificial Intelligence applications and of large language models such as ChatGPT or Bard, demonstrates that the seemingly impossible can quickly become an everyday reality. At present, anyone can purchase online electroencephalogram (EEG) devices for a few hundred dollars [emphasis mine], to measure the electrical activity of their brain for meditation, gaming, or other purposes. [pp. 14-15]

This is very impressive achievement. Some of the research cited was published earlier this year (2023). The extraordinary speed is a testament to the efforts by the authors and their teams. It’s also a testament to how quickly the field is moving.

I’m glad to see the mention of and focus on consumer neurotechnology. (While the authors don’t speculate, I am free to do so.) Consumer neurotechnology could be viewed as one of the steps toward normalizing a cyborg future for all of us. Yes, we have books, television programmes, movies, and video games, which all normalize the idea but the people depicted have been severely injured and require the augmentation. With consumer neurotechnology, you have easily accessible devices being used to enhance people who aren’t injured, they just want to be ‘better’.

This phrase seemed particularly striking “… an important step towards developing the capability to interface human thoughts with computers” in light of some claims made by the Australian military in my June 13, 2023 posting “Mind-controlled robots based on graphene: an Australian research story.” (My posting has an embedded video demonstrating the Brain Robotic Interface (BRI) in action. Also, see the paragraph below the video for my ‘measured’ response.)

There’s no mention of the military in the report which seems more like a deliberate rather than inadvertent omission given the importance of military innovation where technology is concerned.

This section gives a good overview of government initiatives (in the report it’s followed by a table of the programmes),

Thanks to the promises it holds, neurotechnology has garnered significant attention from both governments and the private sector and is considered by many as an investment priority. According to the International Brain Initiative (IBI), brain research funding has become increasingly important over the past ten years, leading to a rise in large-scale state-led programs aimed at advancing brain intervention technologies(International Brain Initiative, 2021). Since 2013, initiatives such as the United States’ Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative and the European Union’s Human Brain Project (HBP), as well as major national initiatives in China, Japan and South Korea have been launched with significant funding support from the respective governments. The Canadian Brain Research Strategy, initially operated as a multi- stakeholder coalition on brain research, is also actively seeking funding support from the government to transform itself into a national research initiative (Canadian Brain Research Strategy, 2022). A similar proposal is also seen in the case of the Australian Brain Alliance, calling for the establishment of an Australian Brain Initiative (Australian Academy of Science, n.d.). [pp. 15-16]

Privacy

There are some concerns such as these,

Beyond the medical realm, research suggests that emotional responses of consumers
related to preferences and risks can be concurrently tracked by neurotechnology, such
as neuroimaging and that neural data can better predict market-level outcomes than
traditional behavioral data (Karmarkar and Yoon, 2016). As such, neural data is
increasingly sought after in the consumer market for purposes such as digital
phenotyping4, neurogaming 5,and neuromarketing6 (UNESCO, 2021). This surge in demand gives rise to risks like hacking, unauthorized data reuse, extraction of privacy-sensitive information, digital surveillance, criminal exploitation of data, and other forms of abuse. These risks prompt the question of whether neural data needs distinct definition and safeguarding measures.

These issues are particularly relevant today as a wide range of electroencephalogram (EEG) headsets that can be used at home are now available in consumer markets for purposes that range from meditation assistance to controlling electronic devices through the mind. Imagine an individual is using one of these devices to play a neurofeedback game, which records the person’s brain waves during the game. Without the person being aware, the system can also identify the patterns associated with an undiagnosed mental health condition, such as anxiety. If the game company sells this data to third parties, e.g. health insurance providers, this may lead to an increase of insurance fees based on undisclosed information. This hypothetical situation would represent a clear violation of mental privacy and of unethical use of neural data.

Another example is in the field of advertising, where companies are increasingly interested in using neuroimaging to better understand consumers’ responses to their products or advertisements, a practice known as neuromarketing. For instance, a company might use neural data to determine which advertisements elicit the most positive emotional responses in consumers. While this can help companies improve their marketing strategies, it raises significant concerns about mental privacy. Questions arise in relation to consumers being aware or not that their neural data is being used, and in the extent to which this can lead to manipulative advertising practices that unfairly exploit unconscious preferences. Such potential abuses underscore the need for explicit consent and rigorous data protection measures in the use of neurotechnology for neuromarketing purposes. [pp. 21-22]

Legalities

Some countries already have laws and regulations regarding neurotechnology data,

At the national level, only a few countries have enacted laws and regulations to protect mental integrity or have included neuro-data in personal data protection laws (UNESCO, University of Milan-Bicocca (Italy) and State University of New York – Downstate Health Sciences University, 2023). Examples are the constitutional reform undertaken by Chile (Republic of Chile, 2021), the Charter for the responsible development of neurotechnologies of the Government of France (Government of France, 2022), and the Digital Rights Charter of the Government of Spain (Government of Spain, 2021). They propose different approaches to the regulation and protection of human rights in relation to neurotechnology. Countries such as the UK are also examining under which circumstances neural data may be considered as a special category of data under the general data protection framework (i.e. UK’s GDPR) (UK’s Information Commissioner’s Office, 2023) [p. 24]

As you can see, these are recent laws. There doesn’t seem to be any attempt here in Canada even though there is an act being reviewed in Parliament that could conceivably include neural data. This is from my May 1, 2023 posting,

Bill C-27 (Digital Charter Implementation Act, 2022) is what I believe is called an omnibus bill as it includes three different pieces of proposed legislation (the Consumer Privacy Protection Act [CPPA], the Artificial Intelligence and Data Act [AIDA], and the Personal Information and Data Protection Tribunal Act [PIDPTA]). [emphasis added July 11, 2023] You can read the Innovation, Science and Economic Development (ISED) Canada summary here or a detailed series of descriptions of the act here on the ISED’s Canada’s Digital Charter webpage.

My focus at the time was artificial intelligence and, now, after reading this UNESCO report and briefly looking at the Innovation, Science and Economic Development (ISED) Canada summary and a detailed series of descriptions of the act on ISED’s Canada’s Digital Charter webpage, I don’t see anything that specifies neural data but it’s not excluded either.

IP5 patents

Here’s the explanation (the footnote is included at the end of the excerpt),

IP5 patents represent a subset of overall patents filed worldwide, which have the
characteristic of having been filed in at least one top intellectual property offices (IPO)
worldwide (the so called IP5, namely the Chinese National Intellectual Property
Administration, CNIPA (formerly SIPO); the European Patent Office, EPO; the Japan
Patent Office, JPO; the Korean Intellectual Property Office, KIPO; and the United States
Patent and Trademark Office, USPTO) as well as another country, which may or may not be an IP5. This signals their potential applicability worldwide, as their inventiveness and industrial viability have been validated by at least two leading IPOs. This gives these patents a sort of “quality” check, also since patenting inventions is costly and if applicants try to protect the same invention in several parts of the world, this normally mirrors that the applicant has expectations about their importance and expected value. If we were to conduct the same analysis using information about individually considered patent applied worldwide, i.e. without filtering for quality nor considering patent families, we would risk conducting a biased analysis based on duplicated data. Also, as patentability standards vary across countries and IPOs, and what matters for patentability is the existence (or not) of prior art in the IPO considered, we would risk mixing real innovations with patents related to catching up phenomena in countries that are not at the forefront of the technology considered.

9 The five IP offices (IP5) is a forum of the five largest intellectual property offices in the world that was set up to improve the efficiency of the examination process for patents worldwide. The IP5 Offices together handle about 80% of the world’s patent applications, and 95% of all work carried out under the Patent Cooperation Treaty (PCT), see http://www.fiveipoffices.org. (Dernis et al., 2015) [p. 31]

AI assistance on this report

As noted earlier I have next to no experience with the analytical tools having not attempted this kind of work in several years. Here’s an example of what they were doing,

We utilize a combination of text embeddings based on Bidirectional Encoder
Representations from Transformer (BERT), dimensionality reduction, and hierarchical
clustering inspired by the BERTopic methodology 12 to identify latent themes within
research literature. Latent themes or topics in the context of topic modeling represent
clusters of words that frequently appear together within a collection of documents (Blei, 2012). These groupings are not explicitly labeled but are inferred through computational analysis examining patterns in word usage. These themes are ‘hidden’ within the text, only to be revealed through this analysis. …

We further utilize OpenAI’s GPT-4 model to enrich our understanding of topics’ keywords and to generate topic labels (OpenAI, 2023), thus supplementing expert review of the broad interdisciplinary corpus. Recently, GPT-4 has shown impressive results in medical contexts across various evaluations (Nori et al., 2023), making it a useful tool to enhance the information obtained from prior analysis stages, and to complement them. The automated process enhances the evaluation workflow, effectively emphasizing neuroscience themes pertinent to potential neurotechnology patents. Notwithstanding existing concerns about hallucinations (Lee, Bubeck and Petro, 2023) and errors in generative AI models, this methodology employs the GPT-4 model for summarization and interpretation tasks, which significantly mitigates the likelihood of hallucinations. Since the model is constrained to the context provided by the keyword collections, it limits the potential for fabricating information outside of the specified boundaries, thereby enhancing the accuracy and reliability of the output. [pp. 33-34]

I couldn’t resist adding the ChatGPT paragraph given all of the recent hoopla about it.

Multimodal neuromodulation and neuromorphic computing patents

I think this gives a pretty good indication of the activity on the patent front,

The largest, coherent topic, termed “multimodal neuromodulation,” comprises 535
patents detailing methodologies for deep or superficial brain stimulation designed to
address neurological and psychiatric ailments. These patented technologies interact with various points in neural circuits to induce either Long-Term Potentiation (LTP) or Long-Term Depression (LTD), offering treatment for conditions such as obsession, compulsion, anxiety, depression, Parkinson’s disease, and other movement disorders. The modalities encompass implanted deep-brain stimulators (DBS), Transcranial Magnetic Stimulation (TMS), and transcranial Direct Current Stimulation (tDCS). Among the most representative documents for this cluster are patents with titles: Electrical stimulation of structures within the brain or Systems and methods for enhancing or optimizing neural stimulation therapy for treating symptoms of Parkinson’s disease and or other movement disorders. [p.65]

Given my longstanding interest in memristors, which (I believe) have to a large extent helped to stimulate research into neuromorphic computing, this had to be included. Then, there was the brain-computer interfaces cluster,

A cluster identified as “Neuromorphic Computing” consists of 366 patents primarily
focused on devices designed to mimic human neural networks for efficient and adaptable computation. The principal elements of these inventions are resistive memory cells and artificial synapses. They exhibit properties similar to the neurons and synapses in biological brains, thus granting these devices the ability to learn and modulate responses based on rewards, akin to the adaptive cognitive capabilities of the human brain.

The primary technology classes associated with these patents fall under specific IPC
codes, representing the fields of neural network models, analog computers, and static
storage structures. Essentially, these classifications correspond to technologies that are key to the construction of computers and exhibit cognitive functions similar to human brain processes.

Examples for this cluster include neuromorphic processing devices that leverage
variations in resistance to store and process information, artificial synapses exhibiting
spike-timing dependent plasticity, and systems that allow event-driven learning and
reward modulation within neuromorphic computers.

In relation to neurotechnology as a whole, the “neuromorphic computing” cluster holds significant importance. It embodies the fusion of neuroscience and technology, thereby laying the basis for the development of adaptive and cognitive computational systems. Understanding this specific cluster provides a valuable insight into the progressing domain of neurotechnology, promising potential advancements across diverse fields, including artificial intelligence and healthcare.

The “Brain-Computer Interfaces” cluster, consisting of 146 patents, embodies a key aspect of neurotechnology that focuses on improving the interface between the brain and external devices. The technology classification codes associated with these patents primarily refer to methods or devices for treatment or protection of eyes and ears, devices for introducing media into, or onto, the body, and electric communication techniques, which are foundational elements of brain-computer interface (BCI) technologies.

Key patents within this cluster include a brain-computer interface apparatus adaptable to use environment and method of operating thereof, a double closed circuit brain-machine interface system, and an apparatus and method of brain-computer interface for device controlling based on brain signal. These inventions mainly revolve around the concept of using brain signals to control external devices, such as robotic arms, and improving the classification performance of these interfaces, even after long periods of non-use.

The inventions described in these patents improve the accuracy of device control, maintain performance over time, and accommodate multiple commands, thus significantly enhancing the functionality of BCIs.

Other identified technologies include systems for medical image analysis, limb rehabilitation, tinnitus treatment, sleep optimization, assistive exoskeletons, and advanced imaging techniques, among others. [pp. 66-67]

Having sections on neuromorphic computing and brain-computer interface patents in immediate proximity led to more speculation on my part. Imagine how much easier it would be to initiate a BCI connection if it’s powered with a neuromorphic (brainlike) computer/device. [ETA July 21, 2023: Following on from that thought, it might be more than just easier to initiate a BCI connection. Could a brainlike computer become part of your brain? Why not? it’s been successfully argued that a robotic wheelchair was part of someone’s body, see my January 30, 2013 posting and scroll down about 40% of the way.)]

Neurotech policy debates

The report concludes with this,

Neurotechnology is a complex and rapidly evolving technological paradigm whose
trajectories have the power to shape people’s identity, autonomy, privacy, sentiments,
behaviors and overall well-being, i.e. the very essence of what it means to be human.

Designing and implementing careful and effective norms and regulations ensuring that neurotechnology is developed and deployed in an ethical manner, for the good of
individuals and for society as a whole, call for a careful identification and characterization of the issues at stake. This entails shedding light on the whole neurotechnology ecosystem, that is what is being developed, where and by whom, and also understanding how neurotechnology interacts with other developments and technological trajectories, especially AI. Failing to do so may result in ineffective (at best) or distorted policies and policy decisions, which may harm human rights and human dignity.

Addressing the need for evidence in support of policy making, the present report offers first time robust data and analysis shedding light on the neurotechnology landscape worldwide. To this end, its proposes and implements an innovative approach that leverages artificial intelligence and deep learning on data from scientific publications and paten[t]s to identify scientific and technological developments in the neurotech space. The methodology proposed represents a scientific advance in itself, as it constitutes a quasi- automated replicable strategy for the detection and documentation of neurotechnology- related breakthroughs in science and innovation, to be repeated over time to account for the evolution of the sector. Leveraging this approach, the report further proposes an IPC-based taxonomy for neurotechnology which allows for a structured framework to the exploration of neurotechnology, to enable future research, development and analysis. The innovative methodology proposed is very flexible and can in fact be leveraged to investigate different emerging technologies, as they arise.

In terms of technological trajectories, we uncover a shift in the neurotechnology industry, with greater emphasis being put on computer and medical technologies in recent years, compared to traditionally dominant trajectories related to biotechnology and pharmaceuticals. This shift warrants close attention from policymakers, and calls for attention in relation to the latest (converging) developments in the field, especially AI and related methods and applications and neurotechnology.

This is all the more important and the observed growth and specialization patterns are unfolding in the context of regulatory environments that, generally, are either not existent or not fit for purpose. Given the sheer implications and impact of neurotechnology on the very essence of human beings, this lack of regulation poses key challenges related to the possible infringement of mental integrity, human dignity, personal identity, privacy, freedom of thought, and autonomy, among others. Furthermore, issues surrounding accessibility and the potential for neurotech enhancement applications triggers significant concerns, with far-reaching implications for individuals and societies. [pp. 72-73]

Last words about the report

Informative, readable, and thought-provoking. And, it helped broaden my understanding of neurotechnology.

Future endeavours?

I’m hopeful that one of these days one of these groups (UNESCO, Canadian Science Policy Centre, or ???) will tackle the issue of business bankruptcy in the neurotechnology sector. It has already occurred as noted in my ““Going blind when your neural implant company flirts with bankruptcy [long read]” April 5, 2022 posting. That story opens with a woman going blind in a New York subway when her neural implant fails. It’s how she found out the company, which supplied her implant was going out of business.

In my July 7, 2023 posting about the UNESCO July 2023 dialogue on neurotechnology, I’ve included information on Neuralink (one of Elon Musk’s companies) and its approval (despite some investigations) by the US Food and Drug Administration to start human clinical trials. Scroll down about 75% of the way to the “Food for thought” subhead where you will find stories about allegations made against Neuralink.

The end

If you want to know more about the field, the report offers a seven-page bibliography and there’s a lot of material here where you can start with this December 3, 2019 posting “Neural and technological inequalities” which features an article mentioning a discussion between two scientists. Surprisingly (to me), the source article is in Fast Company (a leading progressive business media brand), according to their tagline)..

I have two categories you may want to check: Human Enhancement and Neuromorphic Engineering. There are also a number of tags: neuromorphic computing, machine/flesh, brainlike computing, cyborgs, neural implants, neuroprosthetics, memristors, and more.

Should you have any observations or corrections, please feel free to leave them in the Comments section of this posting.

Biohybrid device (a new type of neural implant) could restore limb function

A March 23, 2023 news item on ScienceDaily announces a neural implant that addresses failures due to scarring issues,

Researchers have developed a new type of neural implant that could restore limb function to amputees and others who have lost the use of their arms or legs.

In a study carried out in rats, researchers from the University of Cambridge used the device to improve the connection between the brain and paralysed limbs. The device combines flexible electronics and human stem cells — the body’s ‘reprogrammable’ master cells — to better integrate with the nerve and drive limb function.

Previous attempts at using neural implants to restore limb function have mostly failed, as scar tissue tends to form around the electrodes over time, impeding the connection between the device and the nerve. By sandwiching a layer of muscle cells reprogrammed from stem cells between the electrodes and the living tissue, the researchers found that the device integrated with the host’s body and the formation of scar tissue was prevented. The cells survived on the electrode for the duration of the 28-day experiment, the first time this has been monitored over such a long period.

A March 22, 2023 University of Cambridge press release (also on EurekAlert but published March 23, 2023) by Sarah Collins, delves further into the topic,

The researchers say that by combining two advanced therapies for nerve regeneration – cell therapy and bioelectronics – into a single device, they can overcome the shortcomings of both approaches, improving functionality and sensitivity.

While extensive research and testing will be needed before it can be used in humans, the device is a promising development for amputees or those who have lost function of a limb or limbs. The results are reported in the journal Science Advances.

A huge challenge when attempting to reverse injuries that result in the loss of a limb or the loss of function of a limb is the inability of neurons to regenerate and rebuild disrupted neural circuits.

“If someone has an arm or a leg amputated, for example, all the signals in the nervous system are still there, even though the physical limb is gone,” said Dr Damiano Barone from Cambridge’s Department of Clinical Neurosciences, who co-led the research. “The challenge with integrating artificial limbs, or restoring function to arms or legs, is extracting the information from the nerve and getting it to the limb so that function is restored.”

One way of addressing this problem is implanting a nerve in the large muscles of the shoulder and attaching electrodes to it. The problem with this approach is scar tissue forms around the electrode, plus it is only possible to extract surface-level information from the electrode.

To get better resolution, any implant for restoring function would need to extract much more information from the electrodes. And to improve sensitivity, the researchers wanted to design something that could work on the scale of a single nerve fibre, or axon.

“An axon itself has a tiny voltage,” said Barone. “But once it connects with a muscle cell, which has a much higher voltage, the signal from the muscle cell is easier to extract. That’s where you can increase the sensitivity of the implant.”

The researchers designed a biocompatible flexible electronic device that is thin enough to be attached to the end of a nerve. A layer of stem cells, reprogrammed into muscle cells, was then placed on the electrode. This is the first time that this type of stem cell, called an induced pluripotent stem cell, has been used in a living organism in this way.

“These cells give us an enormous degree of control,” said Barone. “We can tell them how to behave and check on them throughout the experiment. By putting cells in between the electronics and the living body, the body doesn’t see the electrodes, it just sees the cells, so scar tissue isn’t generated.”

The Cambridge biohybrid device was implanted into the paralysed forearm of the rats. The stem cells, which had been transformed into muscle cells prior to implantation, integrated with the nerves in the rat’s forearm. While the rats did not have movement restored to their forearms, the device was able to pick up the signals from the brain that control movement. If connected to the rest of the nerve or a prosthetic limb, the device could help restore movement.

The cell layer also improved the function of the device, by improving resolution and allowing long-term monitoring inside a living organism. The cells survived through the 28-day experiment: the first time that cells have been shown to survive an extended experiment of this kind.

The researchers say that their approach has multiple advantages over other attempts to restore function in amputees. In addition to its easier integration and long-term stability, the device is small enough that its implantation would only require keyhole surgery. Other neural interfacing technologies for the restoration of function in amputees require complex patient-specific interpretations of cortical activity to be associated with muscle movements, while the Cambridge-developed device is a highly scalable solution since it uses ‘off the shelf’ cells.

In addition to its potential for the restoration of function in people who have lost the use of a limb or limbs, the researchers say their device could also be used to control prosthetic limbs by interacting with specific axons responsible for motor control.

“This interface could revolutionise the way we interact with technology,” said co-first author Amy Rochford, from the Department of Engineering. “By combining living human cells with bioelectronic materials, we’ve created a system that can communicate with the brain in a more natural and intuitive way, opening up new possibilities for prosthetics, brain-machine interfaces, and even enhancing cognitive abilities.”

“This technology represents an exciting new approach to neural implants, which we hope will unlock new treatments for patients in need,” said co-first author Dr Alejandro Carnicer-Lombarte, also from the Department of Engineering.

“This was a high-risk endeavour, and I’m so pleased that it worked,” said Professor George Malliaras from Cambridge’s Department of Engineering, who co-led the research. “It’s one of those things that you don’t know whether it will take two years or ten before it works, and it ended up happening very efficiently.”

The researchers are now working to further optimise the devices and improve their scalability. The team have filed a patent application on the technology with the support of Cambridge Enterprise, the University’s technology transfer arm.

The technology relies on opti-oxTM enabled muscle cells. opti-ox is a precision cellular reprogramming technology that enables faithful execution of genetic programmes in cells allowing them to be manufactured consistently at scale. The opti-ox enabled muscle iPSC cell lines used in the experiment were supplied by the Kotter lab [Mark Kotter] from the University of Cambridge. The opti-ox reprogramming technology is owned by synthetic biology company bit.bio.

The research was supported in part by the Engineering and Physical Sciences Research Council (EPSRC), part of UK Research and Innovation (UKRI), Wellcome, and the European Union’s Horizon 2020 Research and Innovation Programme.

Caption: In a study carried out in rats, researchers from the University of Cambridge used a biohybrid device to improve the connection between the brain and paralysed limbs. The device combines flexible electronics and human stem cells – the body’s ‘reprogrammable’ master cells – to better integrate with the nerve and drive limb function. Credit: University of Cambirdge

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

Functional neurological restoration of amputated peripheral nerve using biohybrid regenerative bioelectronics by Amy E. Rochford, Alejandro Carnicer-Lombarte, Malak Kawan, Amy Jin, Sam Hilton, Vincenzo F. Curto, Alexandra L. Rutz, Thomas Moreau, Mark R. N. Kotter, George G. Malliaras, and Damiano G. Barone. Science Advances 22 Mar 2023 Vol 9, Issue 12 DOI: 10.1126/sciadv.add8162

This paper is open access.

The synthetic biology company mentioned in the press release, bit.bio is here

FrogHeart’s 2022 comes to an end as 2023 comes into view

I look forward to 2023 and hope it will be as stimulating as 2022 proved to be. Here’s an overview of the year that was on this blog:

Sounds of science

It seems 2022 was the year that science discovered the importance of sound and the possibilities of data sonification. Neither is new but this year seemed to signal a surge of interest or maybe I just happened to stumble onto more of the stories than usual.

This is not an exhaustive list, you can check out my ‘Music’ category for more here. I have tried to include audio files with the postings but it all depends on how accessible the researchers have made them.

Aliens on earth: machinic biology and/or biological machinery?

When I first started following stories in 2008 (?) about technology or machinery being integrated with the human body, it was mostly about assistive technologies such as neuroprosthetics. You’ll find most of this year’s material in the ‘Human Enhancement’ category or you can search the tag ‘machine/flesh’.

However, the line between biology and machine became a bit more blurry for me this year. You can see what’s happening in the titles listed below (you may recognize the zenobot story; there was an earlier version of xenobots featured here in 2021):

This was the story that shook me,

Are the aliens going to come from outer space or are we becoming the aliens?

Brains (biological and otherwise), AI, & our latest age of anxiety

As we integrate machines into our bodies, including our brains, there are new issues to consider:

  • Going blind when your neural implant company flirts with bankruptcy (long read) April 5, 2022 posting
  • US National Academies Sept. 22-23, 2022 workshop on techno, legal & ethical issues of brain-machine interfaces (BMIs) September 21, 2022 posting

I hope the US National Academies issues a report on their “Brain-Machine and Related Neural Interface Technologies: Scientific, Technical, Ethical, and Regulatory Issues – A Workshop” for 2023.

Meanwhile the race to create brainlike computers continues and I have a number of posts which can be found under the category of ‘neuromorphic engineering’ or you can use these search terms ‘brainlike computing’ and ‘memristors’.

On the artificial intelligence (AI) side of things, I finally broke down and added an ‘artificial intelligence (AI) category to this blog sometime between May and August 2021. Previously, I had used the ‘robots’ category as a catchall. There are other stories but these ones feature public engagement and policy (btw, it’s a Canadian Science Policy Centre event), respectively,

  • “The “We are AI” series gives citizens a primer on AI” March 23, 2022 posting
  • “Age of AI and Big Data – Impact on Justice, Human Rights and Privacy Zoom event on September 28, 2022 at 12 – 1:30 pm EDT” September 16, 2022 posting

These stories feature problems, which aren’t new but seem to be getting more attention,

While there have been issues over AI, the arts, and creativity previously, this year they sprang into high relief. The list starts with my two-part review of the Vancouver Art Gallery’s AI show; I share most of my concerns in part two. The third post covers intellectual property issues (mostly visual arts but literary arts get a nod too). The fourth post upends the discussion,

  • “Mad, bad, and dangerous to know? Artificial Intelligence at the Vancouver (Canada) Art Gallery (1 of 2): The Objects” July 28, 2022 posting
  • “Mad, bad, and dangerous to know? Artificial Intelligence at the Vancouver (Canada) Art Gallery (2 of 2): Meditations” July 28, 2022 posting
  • “AI (artificial intelligence) and art ethics: a debate + a Botto (AI artist) October 2022 exhibition in the Uk” October 24, 2022 posting
  • Should AI algorithms get patents for their inventions and is anyone talking about copyright for texts written by AI algorithms? August 30, 2022 posting

Interestingly, most of the concerns seem to be coming from the visual and literary arts communities; I haven’t come across major concerns from the music community. (The curious can check out Vancouver’s Metacreation Lab for Artificial Intelligence [located on a Simon Fraser University campus]. I haven’t seen any cautionary or warning essays there; it’s run by an AI and creativity enthusiast [professor Philippe Pasquier]. The dominant but not sole focus is art, i.e., music and AI.)

There is a ‘new kid on the block’ which has been attracting a lot of attention this month. If you’re curious about the latest and greatest AI anxiety,

  • Peter Csathy’s December 21, 2022 Yahoo News article (originally published in The WRAP) makes this proclamation in the headline “Chat GPT Proves That AI Could Be a Major Threat to Hollywood Creatives – and Not Just Below the Line | PRO Insight”
  • Mouhamad Rachini’s December 15, 2022 article for the Canadian Broadcasting Corporation’s (CBC) online news overs a more generalized overview of the ‘new kid’ along with an embedded CBC Radio file which runs approximately 19 mins. 30 secs. It’s titled “ChatGPT a ‘landmark event’ for AI, but what does it mean for the future of human labour and disinformation?” The chat bot’s developer, OpenAI, has been mentioned here many times including the previously listed July 28, 2022 posting (part two of the VAG review) and the October 24, 2022 posting.

Opposite world (quantum physics in Canada)

Quantum computing made more of an impact here (my blog) than usual. it started in 2021 with the announcement of a National Quantum Strategy in the Canadian federal government budget for that year and gained some momentum in 2022:

  • “Quantum Mechanics & Gravity conference (August 15 – 19, 2022) launches Vancouver (Canada)-based Quantum Gravity Institute and more” July 26, 2022 posting Note: This turned into one of my ‘in depth’ pieces where I comment on the ‘Canadian quantum scene’ and highlight the appointment of an expert panel for the Council of Canada Academies’ report on Quantum Technologies.
  • “Bank of Canada and Multiverse Computing model complex networks & cryptocurrencies with quantum computing” July 25, 2022 posting
  • “Canada, quantum technology, and a public relations campaign?” December 29, 2022 posting

This one was a bit of a puzzle with regard to placement in this end-of-year review, it’s quantum but it’s also about brainlike computing

It’s getting hot in here

Fusion energy made some news this year.

There’s a Vancouver area company, General Fusion, highlighted in both postings and the October posting includes an embedded video of Canadian-born rapper Baba Brinkman’s “You Must LENR” [L ow E nergy N uclear R eactions or sometimes L attice E nabled N anoscale R eactions or Cold Fusion or CANR (C hemically A ssisted N uclear R eactions)].

BTW, fusion energy can generate temperatures up to 150 million degrees Celsius.

Ukraine, science, war, and unintended consequences

Here’s what you might expect,

These are the unintended consequences (from Rachel Kyte’s, Dean of the Fletcher School, Tufts University, December 26, 2022 essay on The Conversation [h/t December 27, 2022 news item on phys.org]), Note: Links have been removed,

Russian President Vladimir Putin’s war on Ukraine has reverberated through Europe and spread to other countries that have long been dependent on the region for natural gas. But while oil-producing countries and gas lobbyists are arguing for more drilling, global energy investments reflect a quickening transition to cleaner energy. [emphasis mine]

Call it the Putin effect – Russia’s war is speeding up the global shift away from fossil fuels.

In December [2022?], the International Energy Agency [IEA] published two important reports that point to the future of renewable energy.

First, the IEA revised its projection of renewable energy growth upward by 30%. It now expects the world to install as much solar and wind power in the next five years as it installed in the past 50 years.

The second report showed that energy use is becoming more efficient globally, with efficiency increasing by about 2% per year. As energy analyst Kingsmill Bond at the energy research group RMI noted, the two reports together suggest that fossil fuel demand may have peaked. While some low-income countries have been eager for deals to tap their fossil fuel resources, the IEA warns that new fossil fuel production risks becoming stranded, or uneconomic, in the next 20 years.

Kyte’s essay is not all ‘sweetness and light’ but it does provide a little optimism.

Kudos, nanotechnology, culture (pop & otherwise), fun, and a farewell in 2022

This one was a surprise for me,

Sometimes I like to know where the money comes from and I was delighted to learn of the Ărramăt Project funded through the federal government’s New Frontiers in Research Fund (NFRF). Here’s more about the Ărramăt Project from the February 14, 2022 posting,

“The Ărramăt Project is about respecting the inherent dignity and interconnectedness of peoples and Mother Earth, life and livelihood, identity and expression, biodiversity and sustainability, and stewardship and well-being. Arramăt is a word from the Tamasheq language spoken by the Tuareg people of the Sahel and Sahara regions which reflects this holistic worldview.” (Mariam Wallet Aboubakrine)

Over 150 Indigenous organizations, universities, and other partners will work together to highlight the complex problems of biodiversity loss and its implications for health and well-being. The project Team will take a broad approach and be inclusive of many different worldviews and methods for research (i.e., intersectionality, interdisciplinary, transdisciplinary). Activities will occur in 70 different kinds of ecosystems that are also spiritually, culturally, and economically important to Indigenous Peoples.

The project is led by Indigenous scholars and activists …

Kudos to the federal government and all those involved in the Salmon science camps, the Ărramăt Project, and other NFRF projects.

There are many other nanotechnology posts here but this appeals to my need for something lighter at this point,

  • “Say goodbye to crunchy (ice crystal-laden) in ice cream thanks to cellulose nanocrystals (CNC)” August 22, 2022 posting

The following posts tend to be culture-related, high and/or low but always with a science/nanotechnology edge,

Sadly, it looks like 2022 is the last year that Ada Lovelace Day is to be celebrated.

… this year’s Ada Lovelace Day is the final such event due to lack of financial backing. Suw Charman-Anderson told the BBC [British Broadcasting Corporation] the reason it was now coming to an end was:

You can read more about it here:

In the rearview mirror

A few things that didn’t fit under the previous heads but stood out for me this year. Science podcasts, which were a big feature in 2021, also proliferated in 2022. I think they might have peaked and now (in 2023) we’ll see what survives.

Nanotechnology, the main subject on this blog, continues to be investigated and increasingly integrated into products. You can search the ‘nanotechnology’ category here for posts of interest something I just tried. It surprises even me (I should know better) how broadly nanotechnology is researched and applied.

If you want a nice tidy list, Hamish Johnston in a December 29, 2022 posting on the Physics World Materials blog has this “Materials and nanotechnology: our favourite research in 2022,” Note: Links have been removed,

“Inherited nanobionics” makes its debut

The integration of nanomaterials with living organisms is a hot topic, which is why this research on “inherited nanobionics” is on our list. Ardemis Boghossian at EPFL [École polytechnique fédérale de Lausanne] in Switzerland and colleagues have shown that certain bacteria will take up single-walled carbon nanotubes (SWCNTs). What is more, when the bacteria cells split, the SWCNTs are distributed amongst the daughter cells. The team also found that bacteria containing SWCNTs produce a significantly more electricity when illuminated with light than do bacteria without nanotubes. As a result, the technique could be used to grow living solar cells, which as well as generating clean energy, also have a negative carbon footprint when it comes to manufacturing.

Getting to back to Canada, I’m finding Saskatchewan featured more prominently here. They do a good job of promoting their science, especially the folks at the Canadian Light Source (CLS), Canada’s synchrotron, in Saskatoon. Canadian live science outreach events seeming to be coming back (slowly). Cautious organizers (who have a few dollars to spare) are also enthusiastic about hybrid events which combine online and live outreach.

After what seems like a long pause, I’m stumbling across more international news, e.g. “Nigeria and its nanotechnology research” published December 19, 2022 and “China and nanotechnology” published September 6, 2022. I think there’s also an Iran piece here somewhere.

With that …

Making resolutions in the dark

Hopefully this year I will catch up with the Council of Canadian Academies (CCA) output and finally review a few of their 2021 reports such as Leaps and Boundaries; a report on artificial intelligence applied to science inquiry and, perhaps, Powering Discovery; a report on research funding and Natural Sciences and Engineering Research Council of Canada.

Given what appears to a renewed campaign to have germline editing (gene editing which affects all of your descendants) approved in Canada, I might even reach back to a late 2020 CCA report, Research to Reality; somatic gene and engineered cell therapies. it’s not the same as germline editing but gene editing exists on a continuum.

For anyone who wants to see the CCA reports for themselves they can be found here (both in progress and completed).

I’m also going to be paying more attention to how public relations and special interests influence what science is covered and how it’s covered. In doing this 2022 roundup, I noticed that I featured an overview of fusion energy not long before the breakthrough. Indirect influence on this blog?

My post was precipitated by an article by Alex Pasternak in Fast Company. I’m wondering what precipitated Alex Pasternack’s interest in fusion energy since his self-description on the Huffington Post website states this “… focus on the intersections of science, technology, media, politics, and culture. My writing about those and other topics—transportation, design, media, architecture, environment, psychology, art, music … .”

He might simply have received a press release that stimulated his imagination and/or been approached by a communications specialist or publicists with an idea. There’s a reason for why there are so many public relations/media relations jobs and agencies.

Que sera, sera (Whatever will be, will be)

I can confidently predict that 2023 has some surprises in store. I can also confidently predict that the European Union’s big research projects (1B Euros each in funding for the Graphene Flagship and Human Brain Project over a ten year period) will sunset in 2023, ten years after they were first announced in 2013. Unless, the powers that be extend the funding past 2023.

I expect the Canadian quantum community to provide more fodder for me in the form of a 2023 report on Quantum Technologies from the Council of Canadian academies, if nothing else otherwise.

I’ve already featured these 2023 science events but just in case you missed them,

  • 2023 Preview: Bill Nye the Science Guy’s live show and Marvel Avengers S.T.A.T.I.O.N. (Scientific Training And Tactical Intelligence Operative Network) coming to Vancouver (Canada) November 24, 2022 posting
  • September 2023: Auckland, Aotearoa New Zealand set to welcome women in STEM (science, technology, engineering, and mathematics) November 15, 2022 posting

Getting back to this blog, it may not seem like a new year during the first few weeks of 2023 as I have quite the stockpile of draft posts. At this point I have drafts that are dated from June 2022 and expect to be burning through them so as not to fall further behind but will be interspersing them, occasionally, with more current posts.

Most importantly: a big thank you to everyone who drops by and reads (and sometimes even comments) on my posts!!! it’s very much appreciated and on that note: I wish you all the best for 2023.

Going blind when your neural implant company flirts with bankruptcy (long read)

This story got me to thinking about what happens when any kind of implant company (pacemaker, deep brain stimulator, etc.) goes bankrupt or is acquired by another company with a different business model.

As I worked on this piece, more issues were raised and the scope expanded to include prosthetics along with implants while the focus narrowed to neuro as in, neural implants and neuroprosthetics. At the same time, I found salient examples for this posting in other medical advances such as gene editing.

In sum, all references to implants and prosthetics are to neural devices and some issues are illustrated with salient examples from other medical advances (specifically, gene editing).

Definitions (for those who find them useful)

The US Food and Drug Administration defines implants and prosthetics,

Medical implants are devices or tissues that are placed inside or on the surface of the body. Many implants are prosthetics, intended to replace missing body parts. Other implants deliver medication, monitor body functions, or provide support to organs and tissues.

As for what constitutes a neural implant/neuroprosthetic, there’s this from Emily Waltz’s January 20, 2020 article (How Do Neural Implants Work? Neural implants are used for deep brain stimulation, vagus nerve stimulation, and mind-controlled prostheses) for the Institute of Electrical and Electronics Engineers (IEEE) Spectrum magazine,

A neural implant, then, is a device—typically an electrode of some kind—that’s inserted into the body, comes into contact with tissues that contain neurons, and interacts with those neurons in some way.

Now, let’s start with the recent near bankruptcy of a retinal implant company.

The company goes bust (more or less)

From a February 25, 2022 Science Friday (a National Public Radio program) posting/audio file, Note: Links have been removed,

Barbara Campbell was walking through a New York City subway station during rush hour when her world abruptly went dark. For four years, Campbell had been using a high-tech implant in her left eye that gave her a crude kind of bionic vision, partially compensating for the genetic disease that had rendered her completely blind in her 30s. “I remember exactly where I was: I was switching from the 6 train to the F train,” Campbell tells IEEE Spectrum. “I was about to go down the stairs, and all of a sudden I heard a little ‘beep, beep, beep’ sound.’”

It wasn’t her phone battery running out. It was her Argus II retinal implant system powering down. The patches of light and dark that she’d been able to see with the implant’s help vanished.

Terry Byland is the only person to have received this kind of implant in both eyes. He got the first-generation Argus I implant, made by the company Second Sight Medical Products, in his right eye in 2004, and the subsequent Argus II implant in his left 11 years later. He helped the company test the technology, spoke to the press movingly about his experiences, and even met Stevie Wonder at a conference. “[I] went from being just a person that was doing the testing to being a spokesman,” he remembers.

Yet in 2020, Byland had to find out secondhand that the company had abandoned the technology and was on the verge of going bankrupt. While his two-implant system is still working, he doesn’t know how long that will be the case. “As long as nothing goes wrong, I’m fine,” he says. “But if something does go wrong with it, well, I’m screwed. Because there’s no way of getting it fixed.”

Science Friday and the IEEE [Institute of Electrical and Electronics Engineers] Spectrum magazine collaborated to produce this story. You’ll find the audio files and the transcript of interviews with the authors and one of the implant patients in this February 25, 2022 Science Friday (a National Public Radio program) posting.

Here’s more from the February 15, 2022 IEEE Spectrum article by Eliza Strickland and Mark Harris,

Ross Doerr, another Second Sight patient, doesn’t mince words: “It is fantastic technology and a lousy company,” he says. He received an implant in one eye in 2019 and remembers seeing the shining lights of Christmas trees that holiday season. He was thrilled to learn in early 2020 that he was eligible for software upgrades that could further improve his vision. Yet in the early months of the COVID-19 pandemic, he heard troubling rumors about the company and called his Second Sight vision-rehab therapist. “She said, ‘Well, funny you should call. We all just got laid off,’ ” he remembers. She said, ‘By the way, you’re not getting your upgrades.’ ”

These three patients, and more than 350 other blind people around the world with Second Sight’s implants in their eyes, find themselves in a world in which the technology that transformed their lives is just another obsolete gadget. One technical hiccup, one broken wire, and they lose their artificial vision, possibly forever. To add injury to insult: A defunct Argus system in the eye could cause medical complications or interfere with procedures such as MRI scans, and it could be painful or expensive to remove.

The writers included some information about what happened to the business, from the February 15, 2022 IEEE Spectrum article, Note: Links have been removed,

After Second Sight discontinued its retinal implant in 2019 and nearly went out of business in 2020, a public offering in June 2021 raised US $57.5 million at $5 per share. The company promised to focus on its ongoing clinical trial of a brain implant, called Orion, that also provides artificial vision. But its stock price plunged to around $1.50, and in February 2022, just before this article was published, the company announced a proposed merger with an early-stage biopharmaceutical company called Nano Precision Medical (NPM). None of Second Sight’s executives will be on the leadership team of the new company, which will focus on developing NPM’s novel implant for drug delivery.The company’s current leadership declined to be interviewed for this article but did provide an emailed statement prior to the merger announcement. It said, in part: “We are a recognized global leader in neuromodulation devices for blindness and are committed to developing new technologies to treat the broadest population of sight-impaired individuals.”

It’s unclear what Second Sight’s proposed merger means for Argus patients. The day after the merger was announced, Adam Mendelsohn, CEO of Nano Precision Medical, told Spectrum that he doesn’t yet know what contractual obligations the combined company will have to Argus and Orion patients. But, he says, NPM will try to do what’s “right from an ethical perspective.” The past, he added in an email, is “simply not relevant to the new future.”

There may be some alternatives, from the February 15, 2022 IEEE Spectrum article (Note: Links have been removed),

Second Sight may have given up on its retinal implant, but other companies still see a need—and a market—for bionic vision without brain surgery. Paris-based Pixium Vision is conducting European and U.S. feasibility trials to see if its Prima system can help patients with age-related macular degeneration, a much more common condition than retinitis pigmentosa.

Daniel Palanker, a professor of ophthalmology at Stanford University who licensed his technology to Pixium, says the Prima implant is smaller, simpler, and cheaper than the Argus II. But he argues that Prima’s superior image resolution has the potential to make Pixium Vision a success. “If you provide excellent vision, there will be lots of patients,” he tells Spectrum. “If you provide crappy vision, there will be very few.”

Some clinicians involved in the Argus II work are trying to salvage what they can from the technology. Gislin Dagnelie, an associate professor of ophthalmology at Johns Hopkins University School of Medicine, has set up a network of clinicians who are still working with Argus II patients. The researchers are experimenting with a thermal camera to help users see faces, a stereo camera to filter out the background, and AI-powered object recognition. These upgrades are unlikely to result in commercial hardware today but could help future vision prostheses.

The writers have carefully balanced this piece so it is not an outright condemnation of the companies (Second Sight and Nano Precision), from the February 15, 2022 IEEE Spectrum article,

Failure is an inevitable part of innovation. The Argus II was an innovative technology, and progress made by Second Sight may pave the way for other companies that are developing bionic vision systems. But for people considering such an implant in the future, the cautionary tale of Argus patients left in the lurch may make a tough decision even tougher. Should they take a chance on a novel technology? If they do get an implant and find that it helps them navigate the world, should they allow themselves to depend upon it?

Abandoning the Argus II technology—and the people who use it—might have made short-term financial sense for Second Sight, but it’s a decision that could come back to bite the merged company if it does decide to commercialize a brain implant, believes Doerr.

For anyone curious about retinal implant technology (specifically the Argus II), I have a description in a June 30, 2015 posting.

Speculations and hopes for neuroprosthetics

The field of neuroprosthetics is very active. Dr Arthur Saniotis and Prof Maciej Henneberg have written an article where they speculate about the possibilities of a neuroprosthetic that may one day merge with neurons in a February 21, 2022 Nanowerk Spotlight article,

For over a generation several types of medical neuroprosthetics have been developed, which have improved the lives of thousands of individuals. For instance, cochlear implants have restored functional hearing in individuals with severe hearing impairment.

Further advances in motor neuroprosthetics are attempting to restore motor functions in tetraplegic, limb loss and brain stem stroke paralysis subjects.

Currently, scientists are working on various kinds of brain/machine interfaces [BMI] in order to restore movement and partial sensory function. One such device is the ‘Ipsihand’ that enables movement of a paralyzed hand. The device works by detecting the recipient’s intention in the form of electrical signals, thereby triggering hand movement.

Another recent development is the 12 month BMI gait neurohabilitation program that uses a visual-tactile feedback system in combination with a physical exoskeleton and EEG operated AI actuators while walking. This program has been tried on eight patients with reported improvements in lower limb movement and somatic sensation.

Surgically placed electrode implants have also reduced tremor symptoms in individuals with Parkinson’s disease.

Although neuroprosthetics have provided various benefits they do have their problems. Firstly, electrode implants to the brain are prone to degradation, necessitating new implants after a few years. Secondly, as in any kind of surgery, implanted electrodes can cause post-operative infection and glial scarring. Furthermore, one study showed that the neurobiological efficacy of an implant is dependent on the rate of speed of its insertion.

But what if humans designed a neuroprosthetic, which could bypass the medical glitches of invasive neuroprosthetics? However, instead of connecting devices to neural networks, this neuroprosthetic would directly merge with neurons – a novel step. Such a neuroprosthetic could radically optimize treatments for neurodegenerative disorders and brain injuries, and possibly cognitive enhancement [emphasis mine].

A team of three international scientists has recently designed a nanobased neuroprosthetic, which was published in Frontiers in Neuroscience (“Integration of Nanobots Into Neural Circuits As a Future Therapy for Treating Neurodegenerative Disorders“). [open access paper published in 2018]

An interesting feature of their nanobot neuroprosthetic is that it has been inspired from nature by way of endomyccorhizae – a type of plant/fungus symbiosis, which is over four hundred million years old. During endomyccorhizae, fungi use numerous threadlike projections called mycelium that penetrate plant roots, forming colossal underground networks with nearby root systems. During this process fungi take up vital nutrients while protecting plant roots from infections – a win-win relationship. Consequently, the nano-neuroprosthetic has been named ‘endomyccorhizae ligand interface’, or ‘ELI’ for short.

The Spotlight article goes on to describe how these nanobots might function. As for the possibility of cognitive enhancement, I wonder if that might come to be described as a form of ‘artificial intelligence’.

(Dr Arthur Saniotis and Prof Maciej Henneberg are both from the Department of Anthropology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences; and Biological Anthropology and Comparative Anatomy Research Unit, Adelaide Medical School, University of Adelaide. Abdul-Rahman Sawalma who’s listed as an author on the 2018 paper is from the Palestinian Neuroscience Initiative, Al-Quds University, Beit Hanina, Palestine.)

Saniotis and Henneberg’s Spotlight article presents an optimistic view of neuroprosthetics. It seems telling that they cite cochlear implants as a success story when it is viewed by many as ethically fraught (see the Cochlear implant Wikipedia entry; scroll down to ‘Criticism and controversy’).

Ethics and your implants

This is from an April 6, 2015 article by Luc Henry on technologist.eu,

Technologist: What are the potential consequences of accepting the “augmented human” in society?

Gregor Wolbring: There are many that we might not even envision now. But let me focus on failure and obsolescence [emphasis mine], two issues that are rarely discussed. What happens when the mechanisms fails in the middle of an action? Failure has hazardous consequences, but obsolescence has psychological ones. …. The constant surgical inter­vention needed to update the hardware may not be feasible. A person might feel obsolete if she cohabits with others using a newer version.

T. Are researchers working on prosthetics sometimes disconnected from reality?

G. W. Students engaged in the development of prosthetics have to learn how to think in societal terms and develop a broader perspective. Our education system provides them with a fascination for clever solutions to technological challenges but not with tools aiming at understanding the consequences, such as whether their product might increase or decrease social justice.

Wolbring is a professor at the University of Calgary’s Cumming School of Medicine (profile page) who writes on social issues to do with human enhancement/ augmentation. As well,

Some of his areas of engagement are: ability studies including governance of ability expectations, disability studies, governance of emerging and existing sciences and technologies (e.g. nanoscale science and technology, molecular manufacturing, aging, longevity and immortality, cognitive sciences, neuromorphic engineering, genetics, synthetic biology, robotics, artificial intelligence, automatization, brain machine interfaces, sensors), impact of science and technology on marginalized populations, especially people with disabilities he governance of bodily enhancement, sustainability issues, EcoHealth, resilience, ethics issues, health policy issues, human rights and sport.

He also maintains his own website here.

Not just startups

I’d classify Second Sight as a tech startup company and they have a high rate of failure, which may not have been clear to the patients who had the implants. Clinical trials can present problems too as this excerpt from my September 17, 2020 posting notes,

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.”

Symbiosis can be another consequence, as mentioned in my September 17, 2020 posting,

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]

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. [emphasis mine]

It’s complicated

For a lot of people these devices are or could be life-changing. At the same time, there are a number of different issues related to implants/prosthetics; the following is not an exhaustive list. As Wolbring notes, issues that we can’t begin to imagine now are likely to emerge as these medical advances become more ubiquitous.

Ability/disability?

Assistive technologies are almost always portrayed as helpful. For example, a cochlear implant gives people without hearing the ability to hear. The assumption is that this is always a good thing—unless you’re a deaf person who wants to define the problem a little differently. Who gets to decide what is good and ‘normal’ and what is desirable?

While the cochlear implant is the most extreme example I can think of, there are variations of these questions throughout the ‘disability’ communities.

Also, as Wolbring notes in his interview with the Technologist.eu, the education system tends to favour technological solutions which don’t take social issues into account. Wolbring cites social justice issues when he mentions failure and obsolescence.

Technical failures and obsolescence

The story, excerpted earlier in this posting, opened with a striking example of a technical failure at an awkward moment; a blind woman depending on her retinal implant loses all sight as she maneuvers through a subway station in New York City.

Aside from being an awful way to find out the company supplying and supporting your implant is in serious financial trouble and can’t offer assistance or repair, the failure offers a preview of what could happen as implants and prosthetics become more commonly used.

Keeping up/fomo (fear of missing out)/obsolescence

It used to be called ‘keeping up with the Joneses, it’s the practice of comparing yourself and your worldly goods to someone else(‘s) and then trying to equal what they have or do better. Usually, people want to have more and better than the mythical Joneses.

These days, the phenomenon (which has been expanded to include social networking) is better known as ‘fomo’ or fear of missing out (see the Fear of missing out Wikipedia entry).

Whatever you want to call it, humanity’s competitive nature can be seen where technology is concerned. When I worked in technology companies, I noticed that hardware and software were sometimes purchased for features that were effectively useless to us. But, not upgrading to a newer version was unthinkable.

Call it fomo or ‘keeping up with the Joneses’, it’s a powerful force and when people (and even companies) miss out or can’t keep up, it can lead to a sense of inferiority in the same way that having an obsolete implant or prosthetic could.

Social consequences

Could there be a neural implant/neuroprosthetic divide? There is already a digital divide (from its Wikipedia entry),

The digital divide is a gap between those who have access to new technology and those who do not … people without access to the Internet and other ICTs [information and communication technologies] are at a socio-economic disadvantage because they are unable or less able to find and apply for jobs, shop and sell online, participate democratically, or research and learn.

After reading Wolbring’s comments, it’s not hard to imagine a neural implant/neuroprosthetic divide with its attendant psychological and social consequences.

What kind of human am I?

There are other issues as noted in my September 17, 2020 posting. I’ve already mentioned ‘patient 6’, the woman who developed a symbiotic relationship with her brain/computer interface. This is how the relationship ended,

… He [Frederic Gilbert, ethicist] 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.”

Above human

The possibility that implants will not merely restore or endow someone with ‘standard’ sight or hearing or motion or … but will augment or improve on nature was broached in this May 2, 2013 posting, More than human—a bionic ear that extends hearing beyond the usual frequencies and is one of many in the ‘Human Enhancement’ category on this blog.

More recently, Hugh Herr, an Associate Professor at the Massachusetts Institute of Technology (MIT), leader of the Biomechatronics research group at MIT’s Media Lab, a double amputee, and prosthetic enthusiast, starred in the recent (February 23, 2022) broadcast of ‘Augmented‘ on the Public Broadcasting Service (PBS) science programme, Nova.

I found ‘Augmented’ a little offputting as it gave every indication of being an advertisement for Herr’s work in the form of a hero’s journey. I was not able to watch more than 10 mins. This preview gives you a pretty good idea of what it was like although the part in ‘Augmented, where he says he’d like to be a cyborg hasn’t been included,

At a guess, there were a few talking heads (taking up from 10%-20% of the running time) who provided some cautionary words to counterbalance the enthusiasm in the rest of the programme. It’s a standard approach designed to give the impression that both sides of a question are being recognized. The cautionary material is usually inserted past the 1/2 way mark while leaving several minutes at the end for returning to the more optimistic material.

In a February 2, 2010 posting I have excerpts from an article featuring quotes from Herr that I still find startling,

Written by Paul Hochman for Fast Company, Bionic Legs, iLimbs, and Other Super-Human Prostheses [ETA March 23, 2022: an updated version of the article is now on Genius.com] delves further into the world where people may be willing to trade a healthy limb for a prosthetic. From the article,

There are many advantages to having your leg amputated.

Pedicure costs drop 50% overnight. A pair of socks lasts twice as long. But Hugh Herr, the director of the Biomechatronics Group at the MIT Media Lab, goes a step further. “It’s actually unfair,” Herr says about amputees’ advantages over the able-bodied. “As tech advancements in prosthetics come along, amputees can exploit those improvements. They can get upgrades. A person with a natural body can’t.”

Herr is not the only one who favours prosthetics (also from the Hochman article),

This influx of R&D cash, combined with breakthroughs in materials science and processor speed, has had a striking visual and social result: an emblem of hurt and loss has become a paradigm of the sleek, modern, and powerful. Which is why Michael Bailey, a 24-year-old student in Duluth, Georgia, is looking forward to the day when he can amputate the last two fingers on his left hand.

“I don’t think I would have said this if it had never happened,” says Bailey, referring to the accident that tore off his pinkie, ring, and middle fingers. “But I told Touch Bionics I’d cut the rest of my hand off if I could make all five of my fingers robotic.”

But Bailey is most surprised by his own reaction. “When I’m wearing it, I do feel different: I feel stronger. As weird as that sounds, having a piece of machinery incorporated into your body, as a part of you, well, it makes you feel above human.[emphasis mine] It’s a very powerful thing.”

My September 17, 2020 posting touches on more ethical and social issues including some of those surrounding consumer neurotechnologies or brain-computer interfaces (BCI). Unfortunately, I don’t have space for these issues here.

As for Paul Hochman’s article, Bionic Legs, iLimbs, and Other Super-Human Prostheses, now on Genius.com, it has been updated.

Money makes the world go around

Money and business practices have been indirectly referenced (for the most part) up to now in this posting. The February 15, 2022 IEEE Spectrum article and Hochman’s article, Bionic Legs, iLimbs, and Other Super-Human Prostheses, cover two aspects of the money angle.

In the IEEE Spectrum article, a tech start-up company, Second Sight, ran into financial trouble and is acquired by a company that has no plans to develop Second Sight’s core technology. The people implanted with the Argus II technology have been stranded as were ‘patient 6’ and others participating in the clinical trial described in the July 24, 2019 article by Liam Drew for Nature Outlook: The brain mentioned earlier in this posting.

I don’t know anything about the business bankruptcy mentioned in the Drew article but one of the business problems described in the IEEE Spectrum article suggests that Second Sight was founded before answering a basic question, “What is the market size for this product?”

On 18 July 2019, Second Sight sent Argus patients a letter saying it would be phasing out the retinal implant technology to clear the way for the development of its next-generation brain implant for blindness, Orion, which had begun a clinical trial with six patients the previous year. …

“The leadership at the time didn’t believe they could make [the Argus retinal implant] part of the business profitable,” Greenberg [Robert Greenberg, Second Sight co-founder] says. “I understood the decision, because I think the size of the market turned out to be smaller than we had thought.”

….

The question of whether a medical procedure or medicine can be profitable (or should the question be sufficiently profitable?) was referenced in my April 26, 2019 posting in the context of gene editing and personalized medicine

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

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

The ‘Glybera’ story in my July 4, 2019 posting (scroll down about 40% of the way) highlights the issue with “recurring revenue versus chronic therapies,”

Kelly Crowe in a November 17, 2018 article for the CBC (Canadian Broadcasting Corporation) news writes about Glybera,

It is one of this country’s great scientific achievements.

“The first drug ever approved that can fix a faulty gene.

It’s called Glybera, and it can treat a painful and potentially deadly genetic disorder with a single dose — a genuine made-in-Canada medical breakthrough.

But most Canadians have never heard of it.

Here’s my summary (from the July 4, 2019 posting),

It cost $1M for a single treatment and that single treatment is good for at least 10 years.

Pharmaceutical companies make their money from repeated use of their medicaments and Glybera required only one treatment so the company priced it according to how much they would have gotten for repeated use, $100,000 per year over a 10 year period. The company was not able to persuade governments and/or individuals to pay the cost

In the end, 31 people got the treatment, most of them received it for free through clinical trials.

For rich people only?

Megan Devlin’s March 8, 2022 article for the Daily Hive announces a major research investment into medical research (Note: A link has been removed),

Vancouver [Canada] billionaire Chip Wilson revealed Tuesday [March 8, 2022] that he has a rare genetic condition that causes his muscles to waste away, and announced he’s spending $100 million on research to find a cure.

His condition is called facio-scapulo-humeral muscular dystrophy, or FSHD for short. It progresses rapidly in some people and more slowly in others, but is characterized by progressive muscle weakness starting the the face, the neck, shoulders, and later the lower body.

“I’m out for survival of my own life,” Wilson said.

“I also have the resources to do something about this which affects so many people in the world.”

Wilson hopes the $100 million will produce a cure or muscle-regenerating treatment by 2027.

“This could be one of the biggest discoveries of all time, for humankind,” Wilson said. “Most people lose muscle, they fall, and they die. If we can keep muscle as we age this can be a longevity drug like we’ve never seen before.”

According to rarediseases.org, FSHD affects between four and 10 people out of every 100,000 [emphasis mine], Right now, therapies are limited to exercise and pain management. There is no way to stall or reverse the disease’s course.

Wilson is best known for founding athleisure clothing company Lululemon. He also owns the most expensive home in British Columbia, a $73 million mansion in Vancouver’s Kitsilano neighbourhood.

Let’s see what the numbers add up to,

4 – 10 people out of 100,000

40 – 100 people out of 1M

1200 – 3,000 people out of 30M (let’s say this is Canada’s population)\

12,000 – 30,000 people out of 300M (let’s say this is the US’s population)

42,000 – 105,000 out of 1.115B (let’s say this is China’s population)

The rough total comes to 55,200 to 138,000 people between three countries with a combined population total of 1.445B. Given how business currently operates, it seems unlikely that any company will want to offer Wilson’s hoped for medical therapy although he and possibly others may benefit from a clinical trial.

Should profit or wealth be considerations?

The stories about the patients with the implants and the patients who need Glybera are heartbreaking and point to a question not often asked when medical therapies and medications are developed. Is the profit model the best choice and, if so, how much profit?

I have no answer to that question but I wish it was asked by medical researchers and policy makers.

As for wealthy people dictating the direction for medical research, I don’t have answers there either. I hope the research will yield applications and/or valuable information for more than Wilson’s disease.

It’s his money after all

Wilson calls his new venture, SolveFSHD. It doesn’t seem to be affiliated with any university or biomedical science organization and it’s not clear how the money will be awarded (no programmes, no application procedure, no panel of experts). There are three people on the team, Eva R. Chin, scientist and executive director, Chip Wilson, SolveFSHD founder/funder, and FSHD patient, and Neil Camarta, engineer, executive (fossil fuels and clean energy), and FSHD patient. There’s also a Twitter feed (presumably for the latest updates): https://twitter.com/SOLVEFSHD.

Perhaps unrelated but intriguing is news about a proposed new building in Kenneth Chan’s March 31, 2022 article for the Daily Hive,

Low Tide Properties, the real estate arm of Lululemon founder Chip Wilson [emphasis mine], has submitted a new development permit application to build a 148-ft-tall, eight-storey, mixed-use commercial building in the False Creek Flats of Vancouver.

The proposal, designed by local architectural firm Musson Cattell Mackey Partnership, calls for 236,000 sq ft of total floor area, including 105,000 sq ft of general office space, 102,000 sq ft of laboratory space [emphasis mine], and 5,000 sq ft of ground-level retail space. An outdoor amenity space for building workers will be provided on the rooftop.

[next door] The 2001-built, five-storey building at 1618 Station Street immediately to the west of the development site is also owned by Low Tide Properties [emphasis mine]. The Ferguson, the name of the existing building, contains about 79,000 sq ft of total floor area, including 47,000 sq ft of laboratory space and 32,000 sq ft of general office space. Biotechnology company Stemcell technologies [STEMCELL] Technologies] is the anchor tenant [emphasis mine].

I wonder if this proposed new building will house SolveFSHD and perhaps other FSHD-focused enterprises. The proximity of STEMCELL Technologies could be quite convenient. In any event, $100M will buy a lot (pun intended).

The end

Issues I’ve described here in the context of neural implants/neuroprosthetics and cutting edge medical advances are standard problems not specific to these technologies/treatments:

  • What happens when the technology fails (hopefully not at a critical moment)?
  • What happens when your supplier goes out of business or discontinues the products you purchase from them?
  • How much does it cost?
  • Who can afford the treatment/product? Will it only be for rich people?
  • Will this technology/procedure/etc. exacerbate or create new social tensions between social classes, cultural groups, religious groups, races, etc.?

Of course, having your neural implant fail suddenly in the middle of a New York City subway station seems a substantively different experience than having your car break down on the road.

There are, of course, there are the issues we can’t yet envision (as Wolbring notes) and there are issues such as symbiotic relationships with our implants and/or feeling that you are “above human.” Whether symbiosis and ‘implant/prosthetic superiority’ will affect more than a small number of people or become major issues is still to be determined.

There’s a lot to be optimistic about where new medical research and advances are concerned but I would like to see more thoughtful coverage in the media (e.g., news programmes and documentaries like ‘Augmented’) and more thoughtful comments from medical researchers.

Of course, the biggest issue I’ve raised here is about the current business models for health care products where profit is valued over people’s health and well-being. it’s a big question and I don’t see any definitive answers but the question put me in mind of this quote (from a September 22, 2020 obituary for US Supreme Court Justice Ruth Bader Ginsburg by Irene Monroe for Curve),

Ginsburg’s advocacy for justice was unwavering and showed it, especially with each oral dissent. In another oral dissent, Ginsburg quoted a familiar Martin Luther King Jr. line, adding her coda:” ‘The arc of the universe is long, but it bends toward justice,’” but only “if there is a steadfast commitment to see the task through to completion.” …

Martin Luther King Jr. popularized and paraphrased the quote (from a January 18, 2018 article by Mychal Denzel Smith for Huffington Post),

His use of the quote is best understood by considering his source material. “The arc of the moral universe is long, but it bends toward justice” is King’s clever paraphrasing of a portion of a sermon delivered in 1853 by the abolitionist minister Theodore Parker. Born in Lexington, Massachusetts, in 1810, Parker studied at Harvard Divinity School and eventually became an influential transcendentalist and minister in the Unitarian church. In that sermon, Parker said: “I do not pretend to understand the moral universe. The arc is a long one. My eye reaches but little ways. I cannot calculate the curve and complete the figure by experience of sight. I can divine it by conscience. And from what I see I am sure it bends toward justice.”

I choose to keep faith that people will get the healthcare products they need and that all of us need to keep working at making access more fair.

Soft, inflatable, and potentially low-cost neuroprosthetic hand?

An August 16, 2021 news item on ScienceDaily describes a new type of neuroprosthetic,

For the more than 5 million people in the world who have undergone an upper-limb amputation, prosthetics have come a long way. Beyond traditional mannequin-like appendages, there is a growing number of commercial neuroprosthetics — highly articulated bionic limbs, engineered to sense a user’s residual muscle signals and robotically mimic their intended motions.

But this high-tech dexterity comes at a price. Neuroprosthetics can cost tens of thousands of dollars and are built around metal skeletons, with electrical motors that can be heavy and rigid.

Now engineers at MIT [Massachusetts Institute of Technology] and Shanghai Jiao Tong University have designed a soft, lightweight, and potentially low-cost neuroprosthetic hand. Amputees who tested the artificial limb performed daily activities, such as zipping a suitcase, pouring a carton of juice, and petting a cat, just as well as — and in some cases better than — those with more rigid neuroprosthetics.

Here’s a video demonstration,

An August 16, 2021 MIT news news release (also on EurekAlert), which originated the news item, provides more detail,

The researchers found the prosthetic, designed with a system for tactile feedback, restored some primitive sensation in a volunteer’s residual limb. The new design is also surprisingly durable, quickly recovering after being struck with a hammer or run over with a car.

The smart hand is soft and elastic, and weighs about half a pound. Its components total around $500 — a fraction of the weight and material cost associated with more rigid smart limbs.

“This is not a product yet, but the performance is already similar or superior to existing neuroprosthetics, which we’re excited about,” says Xuanhe Zhao, professor of mechanical engineering and of civil and environmental engineering at MIT. “There’s huge potential to make this soft prosthetic very low cost, for low-income families who have suffered from amputation.”

Zhao and his colleagues have published their work today [August 16, 2021] in Nature Biomedical Engineering. Co-authors include MIT postdoc Shaoting Lin, along with Guoying Gu, Xiangyang Zhu, and collaborators at Shanghai Jiao Tong University in China.

Big Hero hand

The team’s pliable new design bears an uncanny resemblance to a certain inflatable robot in the animated film “Big Hero 6.” Like the squishy android, the team’s artificial hand is made from soft, stretchy material — in this case, the commercial elastomer EcoFlex. The prosthetic comprises five balloon-like fingers, each embedded with segments of fiber, similar to articulated bones in actual fingers. The bendy digits are connected to a 3-D-printed “palm,” shaped like a human hand.

Rather than controlling each finger using mounted electrical motors, as most neuroprosthetics do, the researchers used a simple pneumatic system to precisely inflate fingers and bend them in specific positions. This system, including a small pump and valves, can be worn at the waist, significantly reducing the prosthetic’s weight.

Lin developed a computer model to relate a finger’s desired position to the corresponding pressure a pump would have to apply to achieve that position. Using this model, the team developed a controller that directs the pneumatic system to inflate the fingers, in positions that mimic five common grasps, including pinching two and three fingers together, making a balled-up fist, and cupping the palm.

The pneumatic system receives signals from EMG sensors — electromyography sensors that measure electrical signals generated by motor neurons to control muscles. The sensors are fitted at the prosthetic’s opening, where it attaches to a user’s limb. In this arrangement, the sensors can pick up signals from a residual limb, such as when an amputee imagines making a fist.

The team then used an existing algorithm that “decodes” muscle signals and relates them to common grasp types. They used this algorithm to program the controller for their pneumatic system. When an amputee imagines, for instance, holding a wine glass, the sensors pick up the residual muscle signals, which the controller then translates into corresponding pressures. The pump then applies those pressures to inflate each finger and produce the amputee’s intended grasp.

Going a step further in their design, the researchers looked to enable tactile feedback — a feature that is not incorporated in most commercial neuroprosthetics. To do this, they stitched to each fingertip a pressure sensor, which when touched or squeezed produces an electrical signal proportional to the sensed pressure. Each sensor is wired to a specific location on an amputee’s residual limb, so the user can “feel” when the prosthetic’s thumb is pressed, for example, versus the forefinger.

Good grip

To test the inflatable hand, the researchers enlisted two volunteers, each with upper-limb amputations. Once outfitted with the neuroprosthetic, the volunteers learned to use it by repeatedly contracting the muscles in their arm while imagining making five common grasps.

After completing this 15-minute training, the volunteers were asked to perform a number of standardized tests to demonstrate manual strength and dexterity. These tasks included stacking checkers, turning pages, writing with a pen, lifting heavy balls, and picking up fragile objects like strawberries and bread. They repeated the same tests using a more rigid, commercially available bionic hand and found that the inflatable prosthetic was as good, or even better, at most tasks, compared to its rigid counterpart.

One volunteer was also able to intuitively use the soft prosthetic in daily activities, for instance to eat food like crackers, cake, and apples, and to handle objects and tools, such as laptops, bottles, hammers, and pliers. This volunteer could also safely manipulate the squishy prosthetic, for instance to shake someone’s hand, touch a flower, and pet a cat.

In a particularly exciting exercise, the researchers blindfolded the volunteer and found he could discern which prosthetic finger they poked and brushed. He was also able to “feel” bottles of different sizes that were placed in the prosthetic hand, and lifted them in response. The team sees these experiments as a promising sign that amputees can regain a form of sensation and real-time control with the inflatable hand.

The team has filed a patent on the design, through MIT, and is working to improve its sensing and range of motion.

“We now have four grasp types. There can be more,” Zhao says. “This design can be improved, with better decoding technology, higher-density myoelectric arrays, and a more compact pump that could be worn on the wrist. We also want to customize the design for mass production, so we can translate soft robotic technology to benefit society.”

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

A soft neuroprosthetic hand providing simultaneous myoelectric control and tactile feedback by Guoying Gu, Ningbin Zhang, Haipeng Xu, Shaoting Lin, Yang Yu, Guohong Chai, Lisen Ge, Houle Yang, Qiwen Shao, Xinjun Sheng, Xiangyang Zhu, Xuanhe Zhao. Nature Biomedical Engineering (2021) DOI: https://doi.org/10.1038/s41551-021-00767-0 Published: 16 August 2021

This paper is behind a paywall.

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.