Category Archives: human enhancement

The Internet of Bodies and Ghislaine Boddington

I stumbled across this event on my Twitter feed (h/t @katepullinger; Note: Kate Pullinger is a novelist and Professor of Creative Writing and Digital Media, Director of the Centre for Cultural and Creative Industries [CCCI] at Bath Spa University in the UK).

Anyone who visits here with any frequency will have noticed I have a number of articles on technology and the body (you can find them in the ‘human enhancement’ category and/or search fro the machine/flesh tag). Boddington’s view is more expansive than the one I’ve taken and I welcome it. First, here’s the event information and, then, a link to her open access paper from February 2021.

From the CCCI’s Annual Public Lecture with Ghislaine Boddington eventbrite page,

This year’s CCCI Public Lecture will be given by Ghislaine Boddington. Ghislaine is Creative Director of body>data>space and Reader in Digital Immersion at University of Greenwich. Ghislaine has worked at the intersection of the body, the digital, and spatial research for many years. This will be her first in-person appearance since the start of the pandemic, and she will share with us the many insights she has gathered during this extraordinary pivot to online interfaces much of the world has been forced to undertake.

With a background in performing arts and body technologies, Ghislaine is recognised as a pioneer in the exploration of digital intimacy, telepresence and virtual physical blending since the early 90s. As a curator, keynote speaker and radio presenter she has shared her outlook on the future human into the cultural, academic, creative industries and corporate sectors worldwide, examining topical issues with regards to personal data usage, connected bodies and collective embodiment. Her research led practice, examining the evolution of the body as the interface, is presented under the heading ‘The Internet of Bodies’. Recent direction and curation outputs include “me and my shadow” (Royal National Theatre 2012), FutureFest 2015-18 and Collective Reality (Nesta’s FutureFest / SAT Montreal 2016/17). In 2017 Ghislaine was awarded the international IX Immersion Experience Visionary Pioneer Award. She recently co-founded University of Greenwich Strategic Research Group ‘CLEI – Co-creating Liveness in Embodied Immersion’ and is an Associate Editor for AI & Society (Springer). Ghislaine is a long term advocate for diversity and inclusion, working as a Trustee for Stemette Futures and Spokesperson for Deutsche Bank ‘We in Social Tech’ initiative. She is a team member and presenter with BBC World Service flagship radio show/podcast Digital Planet.

Date and time

Thu, 24 June 2021
08:00 – 09:00 [am] PDT

@GBoddington

@bodydataspace

@ConnectedBodies

Boddington’s paper is what ignited my interest; here’s a link to and a citation for it,

The Internet of Bodies—alive, connected and collective: the virtual physical future of our bodies and our senses by Ghislaine Boddington. AI Soc. 2021 Feb 8 : 1–17. DOI: 10.1007/s00146-020-01137-1 PMCID: PMC7868903 PMID: 33584018

Some excerpts from this open access paper,

The Weave—virtual physical presence design—blending processes for the future

Coming from a performing arts background, dance led, in 1989, I became obsessed with the idea that there must be a way for us to be able to create and collaborate in our groups, across time and space, whenever we were not able to be together physically. The focus of my work, as a director, curator and presenter across the last 30 years, has been on our physical bodies and our data selves and how they have, through the extended use of our bodies into digitally created environments, started to merge and converge, shifting our relationship and understanding of our identity and our selfhood.

One of the key methodologies that I have been using since the mid-1990s is inter-authored group creation, a process we called The Weave (Boddington 2013a, b). It uses the simple and universal metaphor of braiding, plaiting or weaving three strands of action and intent, these three strands being:

1. The live body—whether that of the performer, the participant, or the public;

2. The technologies of today—our tools of virtually physical reflection;

3. The content—the theme in exploration.

As with a braid or a plait, the three strands must be weaved simultaneously. What is key to this weave is that in any co-creation between the body and technology, the technology cannot work without the body; hence, there will always be virtual/physical blending. [emphasis mine]

Cyborgs

Cyborg culture is also moving forward at a pace with most countries having four or five cyborgs who have reached out into media status. Manel Munoz is the weather man as such, fascinated and affected by cyclones and anticyclones, his back of the head implant sent vibrations to different sides of his head linked to weather changes around him.

Neil Harbisson from Northern Ireland calls himself a trans-species rather than a cyborg, because his implant is permanently fused into the crown of his head. He is the first trans-species/cyborg to have his passport photo accepted as he exists with his fixed antenna. Neil has, from birth, an eye condition called greyscale, which means he only sees the world in grey and white. He uses his antennae camera to detect colour, and it sends a vibration with a different frequency for each colour viewed. He is learning what colours are within his viewpoint at any given time through the vibrations in his head, a synaesthetic method of transference of one sense for another. Moon Ribas, a Spanish choreographer and a dancer, had two implants placed into the top of her feet, set to sense seismic activity as it occurs worldwide. When a small earthquake occurs somewhere, she received small vibrations; a bigger eruption gives her body a more intense vibration. She dances as she receives and reacts to these transferred data. She feels a need to be closer to our earth, a part of nature (Harbisson et al. 2018).

Medical, non medical and sub-dermal implants

Medical implants, embedded into the body or subdermally (nearer the surface), have rapidly advanced in the last 30 years with extensive use of cardiac pacemakers, hip implants, implantable drug pumps and cochlear implants helping partial deaf people to hear.

Deep body and subdermal implants can be personalised to your own needs. They can be set to transmit chosen aspects of your body data outwards, but they also can receive and control data in return. There are about 200 medical implants in use today. Some are complex, like deep brain stimulation for motor neurone disease, and others we are more familiar with, for example, pacemakers. Most medical implants are not digitally linked to the outside world at present, but this is in rapid evolution.

Kevin Warwick, a pioneer in this area, has interconnected himself and his partner with implants for joint use of their personal and home computer systems through their BrainGate (Warwick 2008) implant, an interface between the nervous system and the technology. They are connected bodies. He works onwards with his experiments to feel the shape of distant objects and heat through fingertip implants.

‘Smart’ implants into the brain for deep brain stimulation are in use and in rapid advancement. The ethics of these developments is under constant debate in 2020 and will be onwards, as is proved by the mass coverage of the Neuralink, Elon Musk’s innovation which connects to the brain via wires, with the initial aim to cure human diseases such as dementia, depression and insomnia and onwards plans for potential treatment of paraplegia (Musk 2016).

Given how many times I’ve featured art/sci (also know as, art/science and/or sciart) and cyborgs and medical implants here, my excitement was a given.

For anyone who wants to pursue Boddington’s work further, her eponymous website is here, the body>data>space is here, and her University of Greenwich profile page is here.

For anyone interested in the Centre for Creative and Cultural Industries (CCCI), their site is here.

Finally, here’s one of my earliest pieces about cyborgs titled ‘My mother is a cyborg‘ from April 20, 2012 and my September 17, 2020 posting titled, ‘Turning brain-controlled wireless electronic prostheses into reality plus some ethical points‘. If you scroll down to the ‘Brain-computer interfaces, symbiosis, and ethical issues’ subhead, you’ll find some article excerpts about a fascinating qualitative study on implants and ethics.

Deus Ex, a video game developer, his art, and reality

The topics of human enhancement and human augmentation have been featured here a number of times from a number of vantage points, including that of a video game seires with some thoughtful story lines known under the Deus Ex banner. (My August 18, 2011 posting, . August 30, 2011 posting, and Sept. 1, 2016 posting are three, which mention Deus Ex in the title but there may be others where the game is noted in the posting.)

A March 19, 2021 posting by Timothy Geigner for Techdirt offers a more fulsome but still brief description of the games along with a surprising declaration (it’s too real) by the game’s creator (Note: Links have been removed),

The Deus Ex franchise has found its way onto Techdirt’s pages a couple of times in the past. If you’re not familiar with the series, it’s a cyberpunk-ish take on the near future with broad themes around human augmentation, and the weaving of broad and famous conspiracy theories. That perhaps makes it somewhat ironic that several of our posts dealing with the franchise have to do with mass media outlets getting confused into thinking its augmentation stories were real life, or the conspiracy theories that centered around leaks for the original game’s sequel were true. The conspiracy theories woven into the original Deus Ex storyline were of the grand variety: takeover of government by biomedical companies pushing a vaccine for a sickness it created, the illuminati, FEMA [US Federal Emergency Management Agency] takeovers, AI-driven surveillance of the public, etc.

And it’s the fact that such conspiracy-driven thinking today led Warren Spector, the creator of the series, to recently state that he probably wouldn’t have created the game today if given the chance. [See pull quote below]

Deus Ex was originally released in 2000 but took place in an alternate 2052 where many of the real world conspiracy theories have come true. The plot included references to vaccinations, black helicopters, FEMA, and ECHELON amongst others, some of which have connotations to real-life events. Spector said, “Interestingly, I’m not sure I’d make Deus Ex today. The conspiracy theories we wrote about are now part of the real world. I don’t want to support that.”

… I’d like to focus on how clearly this illustrates the artistic nature of video games. The desire, or not, to create certain kinds of art due to the reflection such art receives from the broader society is exactly the kind of thing artists operating in other artforms have to deal with. Art imitates life, yes, but in the case of speculative fiction like this, it appears that life can also imitate art. Spector notes that seeing what has happened in the world since Deus Ex was first released in 2000 has had a profound effect on him as an artist. [See pull quote below]

Earlier, Spector had commented on how he was “constantly amazed at how accurate our view of the world ended up being. Frankly it freaks me out a bit.” Some of the conspiracy theories that didn’t end up in the game were those surrounding Denver Airport because they were considered “too silly to include in the game.” These include theories about secret tunnels, connections to aliens and Nazi secret societies, and hidden messages within the airport’s artwork. Spector is now incredulous that they’re “something people actually believe.”

It was possible for Geigner even back to an Oct. 18, 2013 posting to write about a UK newspaper that confused Deus Ex with reality,

… I bring you the British tabloid, The Sun, and their amazing story about an augmented mechanical eyeball that, if associated material is to be believed, allows you to see through walls, color-codes friends and enemies, and permits telescopic zoom. Here’s the reference from The Sun.

Oops. See, part of the reason that Sarif Industries’ cybernetic implants are still in their infancy is that the company doesn’t exist. Sarif Industries is a fictitious company from a cyberpunk video game, Deus Ex, set in a future Detroit. …

There’s more about Spector’s latest comments at a 2021 Game Developers Conference in a March 15, 2021 article by Riley MacLeod for Kotaku. There’s more about Warren Spector here. I always thought Deus Ex was developed by Canadian company, Eidos Montréal and, fter reading the company’s Wikipedia entry, it seems I may have been only partially correct.

Getting back to Deus Ex being ‘too real’, it seems to me that the line between science fiction and reality is increasingly frayed.

BrainGate demonstrates a high-bandwidth wireless brain-computer interface (BCI)

I wrote about some brain computer interface (BCI) work out of Stanford University (California, US), in a Sept. 17, 2020 posting (Turning brain-controlled wireless electronic prostheses into reality plus some ethical points), which may have contributed to what is now the first demonstration of a wireless brain-computer interface for people with tetraplegia (also known as quadriplegia).

From an April 1, 2021 news item on ScienceDaily,

In an important step toward a fully implantable intracortical brain-computer interface system, BrainGate researchers demonstrated human use of a wireless transmitter capable of delivering high-bandwidth neural signals.

Brain-computer interfaces (BCIs) are an emerging assistive technology, enabling people with paralysis to type on computer screens or manipulate robotic prostheses just by thinking about moving their own bodies. For years, investigational BCIs used in clinical trials have required cables to connect the sensing array in the brain to computers that decode the signals and use them to drive external devices.

Now, for the first time, BrainGate clinical trial participants with tetraplegia have demonstrated use of an intracortical wireless BCI with an external wireless transmitter. The system is capable of transmitting brain signals at single-neuron resolution and in full broadband fidelity without physically tethering the user to a decoding system. The traditional cables are replaced by a small transmitter about 2 inches in its largest dimension and weighing a little over 1.5 ounces. The unit sits on top of a user’s head and connects to an electrode array within the brain’s motor cortex using the same port used by wired systems.

For a study published in IEEE Transactions on Biomedical Engineering, two clinical trial participants with paralysis used the BrainGate system with a wireless transmitter to point, click and type on a standard tablet computer. The study showed that the wireless system transmitted signals with virtually the same fidelity as wired systems, and participants achieved similar point-and-click accuracy and typing speeds.

A March 31, 2021 Brown University news release (also on EurekAlert but published April 1, 2021), which originated the news item, provides more detail,

“We’ve demonstrated that this wireless system is functionally equivalent to the wired systems that have been the gold standard in BCI performance for years,” said John Simeral, an assistant professor of engineering (research) at Brown University, a member of the BrainGate research consortium and the study’s lead author. “The signals are recorded and transmitted with appropriately similar fidelity, which means we can use the same decoding algorithms we used with wired equipment. The only difference is that people no longer need to be physically tethered to our equipment, which opens up new possibilities in terms of how the system can be used.”

The researchers say the study represents an early but important step toward a major objective in BCI research: a fully implantable intracortical system that aids in restoring independence for people who have lost the ability to move. While wireless devices with lower bandwidth have been reported previously, this is the first device to transmit the full spectrum of signals recorded by an intracortical sensor. That high-broadband wireless signal enables clinical research and basic human neuroscience that is much more difficult to perform with wired BCIs.

The new study demonstrated some of those new possibilities. The trial participants — a 35-year-old man and a 63-year-old man, both paralyzed by spinal cord injuries — were able to use the system in their homes, as opposed to the lab setting where most BCI research takes place. Unencumbered by cables, the participants were able to use the BCI continuously for up to 24 hours, giving the researchers long-duration data including while participants slept.

“We want to understand how neural signals evolve over time,” said Leigh Hochberg, an engineering professor at Brown, a researcher at Brown’s Carney Institute for Brain Science and leader of the BrainGate clinical trial. “With this system, we’re able to look at brain activity, at home, over long periods in a way that was nearly impossible before. This will help us to design decoding algorithms that provide for the seamless, intuitive, reliable restoration of communication and mobility for people with paralysis.”

The device used in the study was first developed at Brown in the lab of Arto Nurmikko, a professor in Brown’s School of Engineering. Dubbed the Brown Wireless Device (BWD), it was designed to transmit high-fidelity signals while drawing minimal power. In the current study, two devices used together recorded neural signals at 48 megabits per second from 200 electrodes with a battery life of over 36 hours.

While the BWD has been used successfully for several years in basic neuroscience research, additional testing and regulatory permission were required prior to using the system in the BrainGate trial. Nurmikko says the step to human use marks a key moment in the development of BCI technology.

“I am privileged to be part of a team pushing the frontiers of brain-machine interfaces for human use,” Nurmikko said. “Importantly, the wireless technology described in our paper has helped us to gain crucial insight for the road ahead in pursuit of next generation of neurotechnologies, such as fully implanted high-density wireless electronic interfaces for the brain.”

The new study marks another significant advance by researchers with the BrainGate consortium, an interdisciplinary group of researchers from Brown, Stanford and Case Western Reserve universities, as well as the Providence Veterans Affairs Medical Center and Massachusetts General Hospital. In 2012, the team published landmark research in which clinical trial participants were able, for the first time, to operate multidimensional robotic prosthetics using a BCI. That work has been followed by a steady stream of refinements to the system, as well as new clinical breakthroughs that have enabled people to type on computers, use tablet apps and even move their own paralyzed limbs.

“The evolution of intracortical BCIs from requiring a wire cable to instead using a miniature wireless transmitter is a major step toward functional use of fully implanted, high-performance neural interfaces,” said study co-author Sharlene Flesher, who was a postdoctoral fellow at Stanford and is now a hardware engineer at Apple. “As the field heads toward reducing transmitted bandwidth while preserving the accuracy of assistive device control, this study may be one of few that captures the full breadth of cortical signals for extended periods of time, including during practical BCI use.”

The new wireless technology is already paying dividends in unexpected ways, the researchers say. Because participants are able to use the wireless device in their homes without a technician on hand to maintain the wired connection, the BrainGate team has been able to continue their work during the COVID-19 pandemic.

“In March 2020, it became clear that we would not be able to visit our research participants’ homes,” said Hochberg, who is also a critical care neurologist at Massachusetts General Hospital and director of the V.A. Rehabilitation Research and Development Center for Neurorestoration and Neurotechnology. “But by training caregivers how to establish the wireless connection, a trial participant was able to use the BCI without members of our team physically being there. So not only were we able to continue our research, this technology allowed us to continue with the full bandwidth and fidelity that we had before.”

Simeral noted that, “Multiple companies have wonderfully entered the BCI field, and some have already demonstrated human use of low-bandwidth wireless systems, including some that are fully implanted. In this report, we’re excited to have used a high-bandwidth wireless system that advances the scientific and clinical capabilities for future systems.”

Brown has a licensing agreement with Blackrock Microsystems to make the device available to neuroscience researchers around the world. The BrainGate team plans to continue to use the device in ongoing clinical trials.

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

Home Use of a Percutaneous Wireless Intracortical Brain-Computer Interface by Individuals With Tetraplegia by John D Simeral, Thomas Hosman, Jad Saab, Sharlene N Flesher, Marco Vilela, Brian Franco, Jessica Kelemen, David M Brandman, John G Ciancibello, Paymon G Rezaii, Emad N. Eskandar, David M Rosler, Krishna V Shenoy, Jaimie M. Henderson, Arto V Nurmikko, Leigh R. Hochberg. IEEE Transactions on Biomedical Engineering, 2021; 1 DOI: 10.1109/TBME.2021.3069119 Date of Publication: 30 March 2021

This paper is open access.

If you don’t happen to be familiar with the IEEE, it’s the Institute of Electrical and Electronics Engineers. BrainGate can be found here, and Blackrock Microsystems can be found here.

The first story here to feature BrainGate was in a May 17, 2012 posting. (Unfortunately, the video featuring a participant picking up a cup of coffee is no longer embedded in the post.) There’s also an October 31, 2016 posting and an April 24, 2017 posting, both of which mention BrainGate. As for my Sept. 17, 2020 posting (Turning brain-controlled wireless electronic prostheses into reality plus some ethical points), you may want to look at those ethical points.

Toronto’s ArtSci Salon and The Mutant Project March 15, 2021

The Mutant Project is both a book (The Mutant Project: Inside the Global Race to Genetically Modify Humans) and an event about gene editing with special reference to the CRISPR (clustered regularly interspaced short palindromic repeats) twins, Lulu and Nana. The event is being held by Toronto’s ArtSci Salon. Here’s more from their March 3, 2021 announcement (received via email),

The Mutant Project

A talk and discussion with Eben Kirksey

Discussants:

Dr. Elizabeth Koester, Postdoctoral fellow, Department of History, UofT [University of Toronto]

Vincent Auffrey, PhD student, IHPST [Institute for the History and Philosophy of Science and Technology], UofT

Fan Zhang, PhD student, IHPST, UofT

This event will be streamed on Zoom and on Youtube

Here is the link to register to Zoom on the 15th:

https://utoronto.zoom.us/meeting/registe/tZErcemoqzwrG9foNF5Ud86uJXdNeIzQSfDw

Event on FB: https://www.facebook.com/events/4033393163381012/

YouTube: https://www.youtube.com/watch?v=pEFfj3Ovsfk&feature=youtu.be

At a conference in Hong Kong in November 2018, Dr. He Jiankui announced that he had created the first genetically modified babies—twin girls named Lulu and Nana—sending shockwaves around the world. A year later, a Chinese court sentenced Dr. He to three years in prison for “illegal medical practice.”

As scientists elsewhere start to catch up with China’s vast genetic research program, gene editing is fueling an innovation economy that threatens to widen racial and economic inequality. Fundamental questions about science, health, and social justice are at stake: Who gets access to gene editing technologies? As countries loosen regulations around the globe, from the U.S. to Indonesia, can we shape research agendas to promote an ethical and fair society?

Join us to welcome Dr. Kirksey, who will discuss key topics from his book “The Mutant Project”.

The talk will be followed by a Q&A

EBEN KIRKSEY is an American anthropologist who finished his latest book as a Member of the Institute for Advanced Study in Princeton, New Jersey. He has been published in Wired, The Atlantic, The Guardian and The Sunday Times. He is sought out as an expert on science in society by the Associated Press, The Wall Street Journal, The New York Times, Democracy Now, Time and the BBC, among other media outlets. He speaks widely at the world’s leading academic institutions including Oxford, Yale, Columbia, UCLA, and the International Summit of Human Genome Editing, plus music festivals, art exhibits, and community events. Professor Kirksey holds a long-term position at Deakin University in Melbourne, Australia. For more information, please visit https://eben-kirksey.space/.

Elizabeth Koester currently holds a SSHRC [Social Science and Humanities Research Council of Canada] Postdoctoral Fellowship in the Department of History at the University of Toronto. After practising law for many years, she undertook graduate studies in the history of medicine at the Institute for the History and Philosophy of
Science and Technology at the University of Toronto and was awarded a PhD in 2018. A book based on her dissertation, In the Public Good: Eugenics and Law in Ontario, will be published by McGill-Queen’s University Press and is anticipated for Fall 2021.

Vincent Auffrey is pursuing his PhD at the Institute for the History of Philosophy of Science and Technology (IHPST) at the University of Toronto. His focus is set primarily on the social history of medicine and the history of eugenics in Canada. Secondary interests include the histories of scientific racism and of anatomy, and the interplay between knowledge and power.

Fan Zhang is a PhD student at the History of Philosophy of Science and Technology (IHPST) at the University of Toronto

Kirksey’s eponymous website,

Water and minerals have a nanoscale effect on bones

Courtesy: University of Arkansas

What a great image of bones! This December 3, 2020 University of Arkansas news release (also on EurekAlert) by Matt McGowan features research focused on bone material looks exciting. The date for the second study citation and link that I have listed (at the end of this posting) suggests the more recent study may have been initially overlooked in the deluge of COVID-19 research we are experiencing,

University of Arkansas researchers Marco Fielder and Arun Nair have conducted the first study of the combined nanoscale effects of water and mineral content on the deformation mechanisms and thermal properties of collagen, the essence of bone material.

The researchers also compared the results to the same properties of non-mineralized collagen reinforced with carbon nanotubes, which have shown promise as a reinforcing material for bio-composites. This research aids in the development of synthetic materials to mimic bone.

Using molecular dynamics — in this case a computer simulation of the physical movements of atoms and molecules — Nair and Fielder examined the mechanics and thermal properties of collagen-based bio-composites containing different weight percentages of minerals, water and carbon nanotubes when subjected to external loads.

They found that variations of water and mineral content had a strong impact on the mechanical behavior and properties of the bio-composites, the structure of which mimics nanoscale bone composition. With increased hydration, the bio-composites became more vulnerable to stress. Additionally, Nair and Fielder found that the presence of carbon nanotubes in non-mineralized collagen reduced the deformation of the gap regions.

The researchers also tested stiffness, which is the standard measurement of a material’s resistance to deformation. Both mineralized and non-mineralized collagen bio-composites demonstrated less stability with greater water content. Composites with 40% mineralization were twice as strong as those without minerals, regardless of the amount of water content. Stiffness of composites with carbon nanotubes was comparable to that of the mineralized collagen.

“As the degree of mineralization or carbon nanotube content of the collagenous bio-composites increased, the effect of water to change the magnitude of deformation decreased,” Fielder said.

The bio-composites made of collagen and carbon nanotubes were also found to have a higher specific heat than the studied mineralized collagen bio-composites, making them more likely to be resistant to thermal damage that could occur during implantation or functional use of the composite. Like most biological materials, bone is a hierarchical – with different structures at different length scales. At the microscale level, bone is made of collagen fibers, composed of smaller nanofibers called fibrils, which are a composite of collagen proteins, mineralized crystals called apatite and water. Collagen fibrils overlap each other in some areas and are separated by gaps in other areas.

“Though several studies have characterized the mechanics of fibrils, the effects of variation and distribution of water and mineral content in fibril gap and overlap regions are unexplored,” said Nair, who is an associate professor of mechanical engineering. “Exploring these regions builds an understanding of the structure of bone, which is important for uncovering its material properties. If we understand these properties, we can design and build better bio-inspired materials and bio-composites.”

Here are links and citations for both papers mentioned in the news release,

Effects of hydration and mineralization on the deformation mechanisms of collagen fibrils in bone at the nanoscale by Marco Fielder & Arun K. Nair. Biomechanics and Modeling in Mechanobiology volume 18, pages57–68 (2019) Biomech Model Mechanobiol 18, 57–68 (2019). DOI: https://doi.org/10.1007/s10237-018-1067-y First published: 07 August 2018 Issue Date: 15 February 2019

This paper is behind a paywall.

A computational study of mechanical properties of collagen-based bio-composites by Marco Fielder & Arun K. Nair. International Biomechanics Volume 7, 2020 – Issue 1 Pages 76-87 DOI: https://doi.org/10.1080/23335432.2020.1812428 Published online: 02 Sep 2020

This paper is open access.

A fully implantable wireless medical device for patients with severe paralysis

There have been only two people who have tested the device from Australia but the research raises hope, from an Oct, 28, 2020 news item on ScienceDaily,

A tiny device the size of a small paperclip has been shown to help patients with upper limb paralysis to text, email and even shop online in the first human trial.

The device, Stentrode™, has been implanted successfully in two patients, who both suffer from severe paralysis due to amyotrophic lateral sclerosis (ALS) — also known as motor neuron disease (MND) — and neither had the ability to move their upper limbs.

Published in the Journal of NeuroInterventional Surgery, the results found the Stentrode™ was able to wirelessly restore the transmission of brain impulses out of the body. This enabled the patients to successfully complete daily tasks such as online banking, shopping and texting, which previously had not been available to them.

An Oct. 28, 2020 University of Melbourne press release (also on EurekAlert), which originated the news item, fills in some of the detail,

The Royal Melbourne Hospital’s Professor Peter Mitchell, Neurointervention Service Director and principal investigator on the trial, said the findings were promising and demonstrate the device can be safely implanted and used within the patients.

“This is the first time an operation of this kind has been done, so we couldn’t guarantee there wouldn’t be problems, but in both cases the surgery has gone better than we had hoped,” Professor Mitchell said.

Professor Mitchell implanted the device on the study participants through their blood vessels, next to the brain’s motor cortex, in a procedure involving a small ‘keyhole’ incision in the neck.

“The procedure isn’t easy, in each surgery there were differences depending on the patient’s anatomy, however in both cases the patients were able to leave the hospital only a few days later, which also demonstrates the quick recovery from the surgery,” Professor Mitchell said.

Neurointerventionalist and CEO of Synchron – the research commercial partner – Associate Professor Thomas Oxley, said this was a breakthrough moment for the field of brain-computer interfaces.

“We are excited to report that we have delivered a fully implantable, take home, wireless technology that does not require open brain surgery, which functions to restore freedoms for people with severe disability,” Associate Professor Oxley, who is also co-head of the Vascular Bionics Laboratory at the University of Melbourne, said.

The two patients used the Stentrode™ to control the computer-based operating system, in combination with an eye-tracker for cursor navigation. This meant they did not need a mouse or keyboard.

They also undertook machine learning-assisted training to control multiple mouse click actions, including zoom and left click. The first two patients achieved an average click accuracy of 92 per cent and 93 per cent, respectively, and typing speeds of 14 and 20 characters per minute with predictive text disabled.

University of Melbourne Associate Professor Nicholas Opie, co-head of the Vascular Bionics Laboratory at the University and founding chief technology officer of Synchron said the developments were exciting and the patients involved had a level of freedom restored in their lives.

“Observing the participants use the system to communicate and control a computer with their minds, independently and at home, is truly amazing,” Associate Professor Opie said.

“We are thankful to work with such fantastic participants, and my colleagues and I are honoured to make a difference in their lives. I hope others are inspired by their success.

“Over the last eight years we have drawn on some of the world’s leading medical and engineering minds to create an implant that enables people with paralysis to control external equipment with the power of thought. We are pleased to report that we have achieved this.”

The researchers caution that while it is some years away before the technology, capable of returning independence to complete everyday tasks is publicly available, the global, multidisciplinary team is working tirelessly to make this a reality.

The trial recently received a $AU1.48 million grant from the Australian commonwealth government to expand the trial to hospitals in New South Wales and Queensland, with hopes to enrol more patients.

###

About Stentrode™

Stentrode™ was developed by researchers from the University of Melbourne, the Royal Melbourne Hospital, the Florey Institute of Neuroscience and Mental Health, Monash University and the company Synchron Australia – the corporate vehicle established by Associate Professors Thomas Oxley (CEO) and Nicholas Opie (CTO) that aims to develop and commercialise neural bionics technology and products. It draws on some of the world’s leading medical and engineering minds

There’s a little more detail and information in an Oct. 28, 2020 Society of NeuroInterventional Surgery news release on EurekAlert,

Researchers demonstrated the success of a fully implantable wireless medical device, the Stentrode™ brain-computer interface (BCI), designed to allow patients with severe paralysis to resume daily tasks — including texting, emailing, shopping and banking online — without the need for open brain surgery. The first-in-human study was published in the Journal of NeuroInterventional Surgery™, the leading international peer-reviewed journal for the clinical field of neurointerventional surgery.

The patients enrolled in the study utilized the Stentrode neuroprosthesis to control the Microsoft Windows 10 operating system in combination with an eye-tracker for cursor navigation, without a mouse or keyboard. The subjects undertook machine learning-assisted training to control multiple mouse-click actions, including zoom and left click.

“This is a breakthrough moment for the field of brain-computer interfaces. We are excited to report that we have delivered a fully implantable, take home, wireless technology that does not require open brain surgery, which functions to restore freedoms for people with severe disability,” said Thomas Oxley, MD, PhD, and CEO of Synchron, a neurovascular bioelectronics medicine company that conducted the research. “Seeing these first heroic patients resume important daily tasks that had become impossible, such as using personal devices to connect with loved ones, confirms our belief that the Stentrode will one day be able to help millions of people with paralysis.”[1]

Graham Felstead, a 75-year-old man living at home with his wife, has experienced severe paralysis due to amyotrophic lateral sclerosis (ALS). He was the first patient enrolled in the first Stentrode clinical study and the first person to have any BCI implanted via the blood vessels. He received the Stentrode implant in August 2019. With the Stentrode, Felstead was able to remotely contact his spouse, increasing his autonomy and reducing her burden of care. Philip O’Keefe, a 60-year-old man with ALS who works part time, was able to control computer devices to conduct work-related tasks and other independent activities after receiving the Stentrode in April 2020. Functional impairment to his fingers, elbows and shoulders had previously inhibited his ability to engage in these efforts.

The Stentrode device is small and flexible enough to safely pass through curving blood vessels, so the implantation procedure is similar to that of a pacemaker and does not require open brain surgery. Entry through the blood vessels may reduce risk of brain tissue inflammation and rejection of the device, which has been an issue for techniques that require direct brain penetration. Implantation is conducted using well-established neurointerventional techniques that do not require any novel automated robotic assistance.

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

Motor neuroprosthesis implanted with neurointerventional surgery improves capacity for activities of daily living tasks in severe paralysis: first in-human experience by Thomas J Oxley, Peter E Yoo, Gil S Rind, Stephen M Ronayne, C M Sarah Lee, Christin Bird, Victoria Hampshire, Rahul P Sharma, Andrew Morokoff, Daryl L Williams, Christopher MacIsaac, Mark E Howard, Lou Irving, Ivan Vrljic, Cameron Williams, Sam E John, Frank Weissenborn, Madeleine Dazenko, Anna H Balabanski, David Friedenberg, Anthony N Burkitt, Yan T Wong, Katharine J Drummond, Patricia Desmond, Douglas Weber, Timothy Denison, Leigh R Hochberg, Susan Mathers, Terence J O’Brien, Clive N May, J Mocco, David B Grayden, Bruce C V Campbell, Peter Mitchell, Nicholas L Opie. Journal of Neurointerventional Surgery, DOI: http://dx.doi.org/10.1136/neurintsurg-2020-016862 Published Online First: 28 October 2020

This paper is open access.

Gene therapy in Canada; a November 2020 report and two events in December 2020

There’s a lot of action, albeit quiet and understated, in the Canadian gene therapy ‘discussion’. One major boost to the discussion was the Nov. 3, 2020 release of a report by the Canadian Council of Academies (CCA), “From Research to Reality; The Expert Panel on the Approval and Use of Somatic Gene Therapies in Canada.”

Dec. 2 – 3, 2020 Breaking Through

Another boost is the the free and virtual, upcoming 2020 Gairdner Ontario International Symposium “Breaking Through: Delivering on the Promise of Gene Therapy“; an international symposium on gene therapy research and practice, which will feature a presentation on the CCA’s report,

Breaking Through brings together Canadian and international leaders to explore the past, present, and future of somatic gene therapy research and practice. This two-day virtual event will examine the successes, challenges and opportunities from the bench to the bedside. It will also feature:

  • Speaker sessions from Canadian and international researchers at the forefront of gene therapy research.
  • A panel discussion exploring the opportunities and challenges facing Canadian scientists, regulators, clinicians, decision-makers, and patients (Presented by NRC).
  • A presentation and Expert Panel discussion on the Council of Canadian Academies’ latest report, From Research to Reality, and a closing panel discussion about the future of gene therapies and gene editing (Presented by Genome Canada).

The title for the CCA report bears an uncanny resemblance to the name for a Canadian initiative highlighting science research, Research2Reality (R2R). (If you’re curious, you can check out my past postings on R2R by using ‘Research2Reality’ as the term for the blog’s search engine.

Glybera

This name stood out: Michael Hayden (scroll down to his name and click), one of the featured speakers for this Dec. 2 – 3, 2020 event, reminded me of the disturbing Glybera story,

Dr. Hayden identified the first mutations underlying lipoprotein lipase (LPL) deficiency and developed gene therapy approaches to treat this condition, the first approved gene therapy (Glybera) in the western world.

Kelly Crowe’s Nov. 17, 2018 story for the Canadian Broadcasting Corporation (CBC) lays it out,

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.

A team of researchers at the University of British Columbia spent decades developing the treatment for people born with a genetic mutation that causes lipoprotein lipase defficiency (LPLD).

If you have the time, do read Crowe’s Nov. 17, 2018 story but as I warned in another post, it’s heartbreaking.

Fora brief summary, the company which eventually emerged with the licensing rights to Glybera, charged $1m per dose and a single dose is good for 10 years. It seems governments are reluctant to approve the cost and for many individuals, it’s an impossible price to meet, every 10 years. So, the drug is dead. Or perhaps not? Take a look at the symposium’s agenda (scroll down) for description,

GLYBERA REINVENTED: A WINDING STORY OF COMMITMENT, CREATIVITY, AND INNOVATION

Michael Hayden, MB, ChB, PhD, FRCP(C), FRSC, C.M., O.B.C University Killam Professor, Senior Scientist, Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics,

University of British Columbia (Vancouver, BC)

Money issues

One theme from the agenda jumped out at me: money. The focus seems to be largely on accessibility and costs. The Nov. 3, 2020 CCA news release (also on EurekAlert) about the report also prominently featured costs,

Gene therapies are being approved for use in Canada, but could strain healthcare budgets and exacerbate existing treatment inequities [emphasis mine] across the country. However, there are opportunities to control spending, streamline approvals and support fair access through innovation, coordination and collaboration, according to a new expert panel report from the Council of Canadian Academies (CCA).

“Rapid scientific advances mean potentially life-changing treatments are approaching the clinic at an accelerated pace,” said Janet Rossant, PhD, C.C., FRSC, and Chair of the Expert Panel. “These new therapies, however, pose a number of challenges in terms of their introduction into the Canadian healthcare system and ensuring access to those who would most benefit.”

Gene therapies and gene editing

Before moving on, you might find it useful to know (if you don’t already) that gene therapy can be roughly divided into somatic cell gene therapy and germline gene therapy as per the Gene Therapy entry in Wikipedia.

Two other items on the symposium’s agenda (scroll down) drew my attention,

Genome editing and the promise for future therapies

Ronald Cohn, MD, FACMG, FCAHS President and CEO,
The Hospital for Sick Children (SickKids) (Toronto, ON)

COMING SOON: THE FUTURE OF GENE EDITING AND GENE THERAPIES

Presented by: Genome Canada

Rob Annan, PhD President and CEO,
Genome Canada (Ottawa, ON)

R. Alta Charo, J.D. Warren P. Knowles Professor of Law & Bioethics,
University of Wisconsin Law School (Madison, USA)

Jay Ingram, C.M. Science broadcaster and writer, Former Co-Host, Discovery Channel’s “Daily Planet” (Calgary, AB)

Vardit Ravitsky, PhD, FCAHS Full Professor, Bioethics Program, Department of Social and Preventative Medicine, School of Public Health, Université de Montréal; President, International Association of Bioethics (Montréal, QC)

Janet Rossant, PhD, C.C., FRSC President,
Gairdner Foundation (Toronto, ON) [also a member of the CCA expert panel for report on somatic cell therapies ‘From research to reality …’)

Genome editing, by the way and if you don’t know, is also known as gene editing. The presence of the word ‘future’ in both the presentations has my antennae quivering. Could they be hinting at germline editing possibilities? At this time, the research is illegal in Canada.

If you don’t happen to know, somatic gene editing, covered in the CCA report, does not affect future generations as opposed to germline gene editing, which does. Should you be curious about the germline gene editing discussion in Canada, I covered as much information as I could uncover in an April 26, 2019 posting on topic.

Jay Ingram’s presence on the panel sponsored by Genome Canada is a bit of a surprise.

I saw him years ago as the moderator for a panel presentation sponsored by Genome British Columbia. The discussion was about genetics and ethics, which was illustrated by clips from the television programme, ReGenesis (from its IMDB entry),

[Fictional] Geneticist David Sandstrom is the chief scientist at the prestigious virology/micro-biology NORBAC laboratory, a joint enterprise between the USA, Canada and Mexico for countering bio-terrorism.

Ingram (BA in microbiology and an MA that’s not identified in his Wikipedia entry) was a television science presenter for a number of years and has continued to work in the field of science communication. He didn’t seem all that knowledgeable about genetics when he moderated the ReGenesis panel but perhaps his focus will be about the communication element?

For anyone interested in attending the free and virtual “Breaking Through” event, you can register here.

CAR-T cell therapies (a type of somatic cell therapy)

One final note, the first week of December seems to be gene therapy week in Canada. There is another free and virtual event, the second session of the Summit for Cancer Immunotherapy: 2020 Speaker Series (Hosted by BioCanRx, Canada’s Immunotherapy Network), Note: I made a few changes to make this excerpt a bit easier to read,

Session Two: Developing better CAR T-Cell Therapies by engaging patients, performing systematic reviews and assessing real-world and economic evidence
Wednesday, December 9, 1:30 pm – 3:15pm EST [emphasis mine]

Chimeric Antigen Receptor T-cell (CAR-T) therapy is a personalized immunotherapy, currently being assessed in a Canadian Phase I/II clinical trial to test safety and feasibility for relapsed/refractory blood cancer (CD19+ Acute Lymphoblastic Leukemia and non-Hodgkin’s Lymphoma).

This virtual seminar will provide an overview of a multidisciplinary team’s collaborative efforts to synthesize evidence for the development of this clinical trial protocol, using a novel approach (the ‘Excelerator’ model). This approach involved the completion of a systematic review (objective review of existing trial data), engagement of patients and clinicians, and drawing from real world and economic evidence.

Dr. Fergusson will provide a brief introduction. Dr. Kednapa Thavorn will discuss the team’s use of economic modelling to select trial factors to maximize economic feasibility of the therapy, and Mackenzie Wilson (HQP) will discuss the current efforts and future directions to engage diverse stakeholders to inform this work. Gisell Castillo (HQP) will speak about the interviews that were conducted with patients and hematologists to identify potential barriers and enablers to participation and recruitment to the trial.

The team will also discuss two ongoing projects which build on this work. Dr. Lalu will provide an overview on the team’s patient engagement program throughout development of the trial protocol and plans to expand this program to other immunotherapy trials. Joshua Montroy (HQP) will also discuss ongoing work building on the initial systematic review, to use individual participant data meta-analysis to identify factors that may impact the efficacy of CAR-T cell therapy.

Dr. Justin Presseau will moderate the question and answer period.

And there’s this,

Who should attend?

Scientific and health care community including researchers, clinicians and HQP along with patients and caregivers. Note: There will be a plain language overview before the session begins and an opportunity to ask questions after the discussion.

If you want to know more about CAR T-cell therapy, sometimes called gene or cell therapy or immune effect cell therapy, prior to the Dec., 9, 2020 event, this page on the cancer.org website should prove helpful.

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.)

Off-target CRISPR-Cas9 gene-editing changes closer to home than originally believed according to three studies

Heidi Ledford’s June 25, 2020 article (Note: Links have been removed) for Nature focuses on three studies (not yet peer-reviewed) that viewed together suggest CRISPR (clustered regularly interspaced short palindromic repeats) gene-editing is less like using a pair of scissors to cut out unwanted mutations and more like using a catalyst (a chemical agent which increases chemical reactions) and getting unanticipated and unwatned reactions. Except, it’s an unpredictable catalyst.

A suite of experiments that use the gene-editing tool CRISPR–Cas9 to modify human embryos have revealed how the process can make large, unwanted changes to the genome at or near the target site. [emphasis mine]

The studies were published this month on the preprint server bioRxiv, and have not yet been peer-reviewed1,2,3. But taken together, they give scientists a good look at what some say is an underappreciated risk of CRISPR–Cas9 editing. Previous experiments have revealed that the tool can make ‘off target’ gene mutations far from the target site, but the nearby changes identified in the latest studies can be missed by standard assessment methods.

These safety concerns are likely to inform the ongoing debate over whether scientists should edit human embryos to prevent genetic diseases — a process that is controversial because it creates a permanent change to the genome that can be passed down for generations. “If human embryo editing for reproductive purposes or germline editing were space flight, the new data are the equivalent of having the rocket explode at the launch pad before take-off,” says Fyodor Urnov, who studies genome editing at the University of California, Berkeley, but was not involved in any of the latest research.

These studies,if borne out, offer new concerns (from Ledford’s June 25, 2020 article),

The changes are the result of DNA-repair processes harnessed by genome-editing tools. CRISPR–Cas9 uses a small strand of RNA to direct the Cas9 enzyme to a site in the genome with a similar sequence. The enzyme then cuts both strands of DNA at that site, and the cell’s repair systems heal the gap.

The edits occur during that repair: most often, the cell seals up the cut using an error-prone mechanism that can insert or delete a small number of DNA letters. If researchers provide a DNA template, the cell might sometimes use that sequence to mend the cut, resulting in a true rewrite. But broken DNA can also cause shuffling or loss of a large region of the chromosome.

Previous work using CRISPR in mouse embryos and other kinds of human cell had already demonstrated that editing chromosomes can cause large, unwanted effects4,5. But it was important to demonstrate the work in human embryos as well, says Urnov, because different cell types might respond to genome editing differently.

Such rearrangements could be missed in many experiments, which typically look for other unwanted edits, such as single DNA-letter changes or small insertions or deletions of only a few letters. The latest studies, however, looked specifically for large deletions and chromosomal rearrangements near the target site. [emphasis mine] “This is something that all of us in the scientific community will, starting immediately, take more seriously than we already have,” says Urnov. “This is not a one-time fluke.”

Ledford’s article offers some description and analysis of each of the three papers.Note: All of the research was done with nonviable embryos. For anyone who wants to read the papers for themselves here are links and citations for each of the three,

Frequent loss-of-heterozygosity in CRISPR-Cas9-edited early human embryos by Gregorio Alanis-Lobato, Jasmin Zohren, Afshan McCarthy, Norah M.E. Fogarty, Nada Kubikova, Emily Hardman, Maria Greco, Dagan Wells, James M.A. Turner, Kathy K. Niakan. bioRxiv DOI: https://doi.org/10.1101/2020.06.05.135913 Posted: June 5, 2020

Reading frame restoration at the EYS locus, and allele-specific chromosome removal after Cas9 cleavage in human embryos by Michael V. Zuccaro, Jia Xu, Carl Mitchell, Diego Marin, Raymond Zimmerman, Bhavini Rana, Everett Weinstein, Rebeca T. King, Morgan Smith, Stephen H. Tsang, Robin Goland, Maria Jasin, Rogerio Lobo, Nathan Treff, Dieter Egli. bioRxiv DOI: https://doi.org/10.1101/2020.06.17.149237 Posted June 18, 2020

FREQUENT GENE CONVERSION IN HUMAN EMBRYOS INDUCED BY DOUBLE STRAND BREAKS by Dan Liang, Nuria Marti Gutierrez, Tailai Chen, Yeonmi Lee, Sang-Wook Park, Hong Ma, Amy Koski, Riffat Ahmed, Hayley Darby, Ying Li, Crystal Van Dyken, Aleksei Mikhalchenko, Thanasup Gonmanee, Tomonari Hayama, Han Zhao, Keliang Wu, Jingye Zhang, Zhenzhen Hou, Jumi Park, Chong-Jai Kim, Jianhui Gong, Yilin Yuan, Ying Gu, Yue Shen, Susan B. Olson, Hui Yang, David Battaglia, Thomas O’Leary, Sacha A. Krieg, David M. Lee, Diana H. Wu, P. Barton Duell, Sanjiv Kaul, Jin-Soo Kim, Stephen B. Heitner, Eunju Kang, Zi-Jiang Chen, Paula Amato, Shoukhrat Mitalipov. bioRxiv DOI: https://doi.org/10.1101/2020.06.19.162214 Posted June 20, 2020

These papers are open access.

A July 17, 2018 posting is probably the first time I featured work showing that CRISPR gene-editing can result in off-target effects; it was followed up by a September 20, 2019 posting on the topic.

July 2020 update on Dr. He Jiankui (the CRISPR twins) situation

This was going to be written for January 2020 but sometimes things happen (e.g., a two-part overview of science culture in Canada from 2010-19 morphed into five parts with an addendum and, then, a pandemic). By now (July 28, 2020), Dr. He’s sentencing to three years in jail announced by the Chinese government in January 2020 is old news.

Regardless, it seems a neat and tidy ending to an international scientific scandal concerned with germline-editing which resulted in at least one set of twins, Lulu and Nana. He claimed to have introduced a variant (“Delta 32” variation) of their CCR5 gene. This does occur naturally and scientists have noted that people with this mutation seem to be resistant to HIV and smallpox.

For those not familiar with the events surrounding the announcement, here’s a brief recap. News of the world’s first gene-edited twins’ birth was announced in November 2018 just days before an international meeting group of experts who had agreed on a moratorium in 2015 on exactly that kind of work. The scientist making the announcement about the twins was scheduled for at least one presentation at the meeting, which was to be held in Hong Kong. He did give his presentation but left the meeting shortly afterwards as shock was beginning to abate and fierce criticism was rising. My November 28, 2018 posting (First CRISPR gene-edited babies? Ethics and the science story) offers a timeline of sorts and my initial response.

I subsequently followed up with two mores posts as the story continued to develop. My May 17, 2019 posting (Genes, intelligence, Chinese CRISPR (clustered regularly interspaced short palindromic repeats) babies, and other children) featured news that Dr. He’s gene-editing may have resulted in the twins having improved cognitive skills. Then, more news broke. The title for my June 20, 2019 posting (Greater mortality for the CRISPR twins Lulu and Nana?) is self-explanatory.

I have roughly organized my sources for this posting into two narratives, which I’m contrasting with each other. First, there is one found in the mainstream media (English language), ‘The Popular Narrative’. Second, there is story where Dr. He is viewed more sympathetically and as part of a larger community where there isn’t nearly as much consensus over what should or shouldn’t be done as ‘the popular narrative’ insists.

The popular narrative: Dr. He was a rogue scientist

A December 30, 2019 article for Fast Company by Kristin Toussaint lays out the latest facts (Note: A link has been removed),

… Now, a court in China has sentenced He to three years in prison, according to Xinhua, China’s state-run press agency, for “illegal medical practices.”

The court in China’s southern city of Shenzhen says that He’s team, which included colleagues Zhang Renli and Qin Jinzhou from two medical institutes in Guangdong Province, falsified ethical approval documents and violated China’s “regulations and ethical principles” with their gene-editing work. Zhang was sentenced to two years in jail, and Qin to 18 months with a two-year reprieve, according to Xinhau.

Ian Sample’s December 31, 2020 article for the Guardian offers more detail (Note: Links have been removed),

The court in Shenzhen found He guilty of “illegal medical practices” and in addition to the prison sentence fined him 3m yuan (£327,360), according to the state news agency, Xinhua. Two others on He’s research team received lesser fines and sentences.

“The three accused did not have the proper certification to practise medicine, and in seeking fame and wealth, deliberately violated national regulations in scientific research and medical treatment,” the court said, according to Xinhua. “They’ve crossed the bottom line of ethics in scientific research and medical ethics.”

[…] the court found He had forged documents from an ethics review panel that were used to recruit couples for the research. The couples that enrolled had a man with HIV and a woman without and were offered IVF in return for taking part.

Zhang Renli, who worked with He, was sentenced to two years in prison and fined 1m yuan. Colleague Qin Jinzhou received an 18-month sentence, but with a two-year reprieve, and a 500,000 yuan fine.

He’s experiments, which were carried out on seven embryos in late 2018, sent shockwaves through the medical and scientific world. The work was swiftly condemned for deceiving vulnerable patients and using a risky, untested procedure with no medical justification. Earlier this month, MIT Technology Review released excerpts from an early manuscript of He’s work. It casts serious doubts on his claims to have made the children immune to HIV.

Even as the scientific community turned against He, the scientist defended his work and said he was proud of having created Lulu and Nana. A third child has since been born as a result of the experiments.

Robin Lovell-Badge at the Francis Crick Institute in London said it was “far too premature” for anyone to pursue genome editing on embryos that are intended to lead to pregnancies. “At this stage we do not know if the methods will ever be sufficiently safe and efficient, although the relevant science is progressing rapidly, and new methods can look promising. It is also important to have standards established, including detailed regulatory pathways, and appropriate means of governance.”

A December 30, 2019 article, by Carolyn Y. Johnson for the Washington Post, covers much the same ground although it does go on to suggest that there might be some blame to spread around (Note: Links have been removed),

The Chinese researcher who stunned and alarmed the international scientific community with the announcement that he had created the world’s first gene-edited babies has been sentenced to three years in prison by a court in China.

He Jiankui sparked a bioethical crisis last year when he claimed to have edited the DNA of human embryos, resulting in the birth of twins called Lulu and Nana as well as a possible third pregnancy. The gene editing, which was aimed at making the children immune to HIV, was excoriated by many scientists as a reckless experiment on human subjects that violated basic ethical principles.

The judicial proceedings were not public, and outside experts said it is hard to know what to make of the punishment without the release of the full investigative report or extensive knowledge of Chinese law and the conditions under which He will be incarcerated.

Jennifer Doudna, a biochemist at the University of California at Berkeley who co-invented CRISPR, the gene editing technology that He utilized, has been outspoken in condemning the experiments and has repeatedly said CRISPR is not ready to be used for reproductive purposes.

R. Alta Charo, a fellow at Stanford’s Center for Advanced Study in the Behavioral Sciences, was among a small group of experts who had dinner with He the night before he unveiled his controversial research in Hong Kong in November 2018.

“He Jiankui is an example of somebody who fundamentally didn’t understand, or didn’t want to recognize, what have become international norms around responsible research,” Charo said. “My impression is he allowed his personal ambition to completely cloud rational thinking and judgment.”

Scientists have been testing an array of powerful biotechnology tools to fix genetic diseases in adults. There is tremendous excitement about the possibility of fixing genes that cause serious disease, and the first U.S. patients were treated with CRISPR this year.

But scientists have long drawn a clear moral line between curing genetic diseases in adults and editing and implanting human embryos, which raises the specter of “designer babies.” Those changes and any unanticipated ones could be inherited by future generations — in essence altering the human species.

“The fact that the individual at the center of the story has been punished for his role in it should not distract us from examining what supporting roles were played by others, particularly in the international scientific community and also the environment that shaped and encouraged him to push the limits,” said Benjamin Hurlbut [emphasis mine], associate professor in the School of Life Sciences at Arizona State University.

Stanford University cleared its scientists, including He’s former postdoctoral adviser, Stephen Quake, finding that Quake and others did not participate in the research and had expressed “serious concerns to Dr. He about his work.” A Rice University spokesman said an investigation continues into bioengineering professor Michael Deem, He’s former academic adviser. Deem was listed as a co-author on a paper called “Birth of Twins After Genome Editing for HIV Resistance,” submitted to scientific journals, according to MIT Technology Review.

It’s interesting that it’s only the Chinese scientists who are seen to be punished, symbolically at least. Meanwhile, Stanford clears its scientists of any wrongdoing and Rice University continues to investigate.

Watch for the Hurlbut name (son, Benjamin and father, William) to come up again in the ‘complex narrative’ section.

Criticism of the ‘twins’ CRISPR editing’ research

Antonio Regalado’s December 3, 2020 article for the MIT (Massachusetts Institute of Technology) Technology Review features comments from various experts on an unpublished draft of Dr. He Jiankui’s research

Earlier this year a source sent us a copy of an unpublished manuscript describing the creation of the first gene-edited babies, born last year in China. Today, we are making excerpts of that manuscript public for the first time.

Titled “Birth of Twins After Genome Editing for HIV Resistance,” and 4,699 words long, the still unpublished paper was authored by He Jiankui, the Chinese biophysicist who created the edited twin girls. A second manuscript we also received discusses laboratory research on human and animal embryos.

The metadata in the files we were sent indicate that the two draft papers were edited by He in late November 2018 and appear to be what he initially submitted for publication. Other versions, including a combined manuscript, may also exist. After consideration by at least two prestigious journals, Nature and JAMA, his research remains unpublished.

The text of the twins paper is replete with expansive claims of a medical breakthrough that can “control the HIV epidemic.” It claims “success”—a word used more than once—in using a “novel therapy” to render the girls resistant to HIV. Yet surprisingly, it makes little attempt to prove that the twins really are resistant to the virus. And the text largely ignores data elsewhere in the paper suggesting that the editing went wrong.

We shared the unpublished manuscripts with four experts—a legal scholar, an IVF doctor, an embryologist, and a gene-editing specialist—and asked them for their reactions. Their views were damning. Among them: key claims that He and his team made are not supported by the data; the babies’ parents may have been under pressure to agree to join the experiment; the supposed medical benefits are dubious at best; and the researchers moved forward with creating living human beings before they fully understood the effects of the edits they had made.

1. Why aren’t the doctors among the paper’s authors?

The manuscript begins with a list of the authors—10 of them, mostly from He Jiankui’s lab at the Southern University of Science and Technology, but also including Hua Bai, director of an AIDS support network, who helped recruit couples, and Michael Deem, an American biophysicist whose role is under review by Rice University. (His attorney previously said Deem never agreed to submit the manuscript and sought to remove his name from it.)

It’s a small number of people for such a significant project, and one reason is that some names are missing—notably, the fertility doctors who treated the patients and the obstetrician who delivered the babies. Concealing them may be an attempt to obscure the identities of the patients. However, it also leaves unclear whether or not these doctors understood they were helping to create the first gene-edited babies.

To some, the question of whether the manuscript is trustworthy arises immediately.

Hank Greely, professor of law, Stanford University: We have no, or almost no, independent evidence for anything reported in this paper. Although I believe that the babies probably were DNA-edited and were born, there’s very little evidence for that. Given the circumstances of this case, I am not willing to grant He Jiankui the usual presumption of honesty. 

That last article by Regalado is the purest example I have of how fierce the criticism is and how almost all of it is focused on Dr. He and his Chinese colleagues.

A complex, measured narrative: multiple players in the game

The most sympathetic and, in many ways, the most comprehensive article is an August 1, 2019 piece by Jon Cohen for Science magazine (Note: Links have been removed),

On 10 June 2017, a sunny and hot Saturday in Shenzhen, China, two couples came to the Southern University of Science and Technology (SUSTech) to discuss whether they would participate in a medical experiment that no researcher had ever dared to conduct. The Chinese couples, who were having fertility problems, gathered around a conference table to meet with He Jiankui, a SUSTech biophysicist. Then 33, He (pronounced “HEH”) had a growing reputation in China as a scientist-entrepreneur but was little known outside the country. “We want to tell you some serious things that might be scary,” said He, who was trim from years of playing soccer and wore a gray collared shirt, his cuffs casually unbuttoned.

He simply meant the standard in vitro fertilization (IVF) procedures. But as the discussion progressed, He and his postdoc walked the couples through informed consent forms [emphasis mine] that described what many ethicists and scientists view as a far more frightening proposition. Seventeen months later, the experiment triggered an international controversy, and the worldwide scientific community rejected him. The scandal cost him his university position and the leadership of a biotech company he founded. Commentaries labeled He, who also goes by the nickname JK, a “rogue,” “China’s Frankenstein,” and “stupendously immoral.” [emphases mine]

But that day in the conference room, He’s reputation remained untarnished. As the couples listened and flipped through the forms, occasionally asking questions, two witnesses—one American, the other Chinese—observed [emphasis mine]. Another lab member shot video, which Science has seen [emphasis mine], of part of the 50-minute meeting. He had recruited those couples because the husbands were living with HIV infections kept under control by antiviral drugs. The IVF procedure would use a reliable process called sperm washing to remove the virus before insemination, so father-to-child transmission was not a concern. Rather, He sought couples who had endured HIV-related stigma and discrimination and wanted to spare their children that fate by dramatically reducing their risk of ever becoming infected. [emphasis mine]

He, who for much of his brief career had specialized in sequencing DNA, offered a potential solution: CRISPR, the genome-editing tool that was revolutionizing biology, could alter a gene in IVF embryos to cripple production of an immune cell surface protein, CCR5, that HIV uses to establish an infection. “This technique may be able to produce an IVF baby naturally immunized against AIDS,” one consent form read.[emphasis mine]

The couples’ children could also pass the protective mutation to future generations. The prospect of this irrevocable genetic change is why, since the advent of CRISPR as a genome editor 5 years earlier, the editing of human embryos, eggs, or sperm has been hotly debated. The core issue is whether such germline editing would cross an ethical red line because it could ultimately alter our species. Regulations, some with squishy language, arguably prohibited it in many countries, China included.

Yet opposition was not unanimous. A few months before He met the couples, a committee convened by the U.S. National Academies of Sciences, Engineering, and Medicine (NASEM) concluded in a well-publicized report that human trials of germline editing “might be permitted” if strict criteria were met. The group of scientists, lawyers, bioethicists, and patient advocates spelled out a regulatory framework but cautioned that “these criteria are necessarily vague” because various societies, caregivers, and patients would view them differently. The committee notably did not call for an international ban, arguing instead for governmental regulation as each country deemed appropriate and “voluntary self-regulation pursuant to professional guidelines.”

[…] He hid his plans and deceived his colleagues and superiors, as many people have asserted? A preliminary investigation in China stated that He had forged documents, “dodged supervision,” and misrepresented blood tests—even though no proof of those charges was released [emphasis mine], no outsiders were part of the inquiry, and He has not publicly admitted to any wrongdoing. (CRISPR scientists in China say the He fallout has affected their research.) Many scientists outside China also portrayed He as a rogue actor. “I think there has been a failure of self-regulation by the scientific community because of a lack of transparency,” virologist David Baltimore, a Nobel Prize–winning researcher at the California Institute of Technology (Caltech) in Pasadena and co-chair of the Hong Kong summit, thundered at He after the biophysicist’s only public talk on the experiment.

Because the Chinese government has revealed little and He is not talking, key questions about his actions are hard to answer. Many of his colleagues and confidants also ignored Science‘s requests for interviews. But Ryan Ferrell, a public relations specialist He hired, has cataloged five dozen people who were not part of the study but knew or suspected what He was doing before it became public. Ferrell calls it He’s circle of trust. [emphasis mine]

That circle included leading scientists—among them a Nobel laureate—in China and the United States, business executives, an entrepreneur connected to venture capitalists, authors of the NASEM report, a controversial U.S. IVF specialist [John Zhang] who discussed opening a gene-editing clinic with He [emphasis mine], and at least one Chinese politician. “He had an awful lot of company to be called a ‘rogue,’” says geneticist George Church [emphases mine], a CRISPR pioneer at Harvard University who was not in the circle of trust and is one of the few scientists to defend at least some aspects of He’s experiment.

Some people sharply criticized He when he brought them into the circle; others appear to have welcomed his plans or did nothing. Several went out of their way to distance themselves from He after the furor erupted. For example, the two onlookers in that informed consent meeting were Michael Deem, He’s Ph.D. adviser at Rice University in Houston, Texas, and Yu Jun, a member of the Chinese Academy of Sciences (CAS) and co-founder of the Beijing Genomics Institute, the famed DNA sequencing company in Shenzhen. Deem remains under investigation by Rice for his role in the experiment and would not speak with Science. In a carefully worded statement, Deem’s lawyers later said he “did not meet the parents of the reported CCR5-edited children, or anyone else whose embryos were edited.” But earlier, Deem cooperated with the Associated Press (AP) for its exclusive story revealing the birth of the babies, which reported that Deem was “present in China when potential participants gave their consent and that he ‘absolutely’ thinks they were able to understand the risks. [emphasis mine]”

Yu, who works at CAS’s Beijing Institute of Genomics, acknowledges attending the informed consent meeting with Deem, but he told Science he did not know that He planned to implant gene-edited embryos. “Deem and I were chatting about something else,” says Yu, who has sequenced the genomes of humans, rice, silkworms, and date palms. “What was happening in the room was not my business, and that’s my personality: If it’s not my business, I pay very little attention.”

Some people who know He and have spoken to Science contend it is time for a more open discussion of how the biophysicist formed his circle of confidants and how the larger circle of trust—the one between the scientific community and the public—broke down. Bioethicist William Hurlbut at Stanford University [emphasis mine] in Palo Alto, California, who knew He wanted to conduct the embryo-editing experiment and tried to dissuade him, says that He was “thrown under the bus” by many people who once supported him. “Everyone ran for the exits, in both the U.S. and China. I think everybody would do better if they would just openly admit what they knew and what they did, and then collectively say, ‘Well, people weren’t clear what to do. We should all admit this is an unfamiliar terrain.’”

Steve Lombardi, a former CEO of Helicos, reacted far more charitably. Lombardi, who runs a consulting business in Bridgewater, Connecticut, says Quake introduced him to He to help find investors for Direct Genomics. “He’s your classic, incredibly bright, naïve entrepreneur—I run into them all the time,” Lombardi says. “He had the right instincts for what to do in China and just didn’t know how to do it. So I put him in front of as many people as I could.” Lombardi says He told him about his embryo-editing ambitions in August 2017, asking whether Lombardi could find investors for a new company that focused on “genetic medical tourism” and was based in China or, because of a potentially friendlier regulatory climate, Thailand. “I kept saying to him, ‘You know, you’ve got to deal with the ethics of this and be really sure that you know what you’re doing.’”

In April 2018, He asked Ferrell to handle his media full time. Ferrell was a good fit—he had an undergraduate degree in neuroscience, had spent a year in Beijing studying Chinese, and had helped another company using a pre-CRISPR genome editor. Now that a woman in the trial was pregnant, Ferrell says, He’s “understanding of the gravity of what he had done increased.” Ferrell had misgivings about the experiment, but he quit HDMZ and that August moved to Shenzhen. With the pregnancy already underway, Ferrell reasoned, “It was going to be the biggest science story of that week or longer, no matter what I did.”

MIT Technology Review had broken a story early that morning China time, saying human embryos were being edited and implanted, after reporter Antonio Regalado discovered descriptions of the project that He had posted online, without Ferrell’s knowledge, in an official Chinese clinical trial registry. Now, He gave AP the green light to post a detailed account, which revealed that twin girls—whom He, to protect their identifies, named Lulu and Nana—had been born. Ferrell and He also posted five unfinished YouTube videos explaining and justifying the unprecedented experiment.

“He was fearful that he’d be unable to communicate to the press and the onslaught in a way that would be in any way manageable for him,” Ferrell says. One video tried to forestall eugenics accusations, with He rejecting goals such as enhancing intelligence, changing skin color, and increasing sports performance as “not love.” Still, the group knew it had lost control of the news. [emphasis mine]

… On 7 March 2017, 5 weeks after the California gathering, He submitted a medical ethics approval application to the Shenzhen HarMoniCare Women and Children’s Hospital that outlined the planned CCR5 edit of human embryos. The babies, it claimed, would be resistant to HIV as well as to smallpox and cholera. (The natural CCR5 mutation may have been selected for because it helps carriers survive smallpox and plague, some studies suggest—but they don’t mention cholera.) “This is going to be a great science and medicine achievement ever since the IVF technology which was awarded the Nobel Prize in 2010, and will also bring hope to numerous genetic disease patients,” the application says. Seven people on the ethics committee, chaired by Lin Zhitong—a one-time Direct Genomics director and a HarMoniCare administrator—signed the application, indicating they approved it.

[…] John Zhang, […] [emphasis mine] earned his medical degree in China and a Ph.D. in reproductive biology at the University of Cambridge in the United Kingdom. Zhang had made international headlines himself in September 2016, when New Scientist revealed that he had created the world’s first “three-parent baby” by using mitochondrial DNA from a donor egg to revitalize the egg of a woman with infertility and then inseminating the resulting egg. “This technology holds great hope for ladies with advanced maternal age to have their own children with their own eggs,” Zhang explains in the center’s promotional video, which alternates between Chinese and English. It does not mention that Zhang did the IVF experiment in Mexico because it is not now allowed in the United States. [emphasis mine]

When Science contacted Zhang, the physician initially said he barely knew He: [emphases mine] “I know him just like many people know him, in an academic meeting.”

After his talk [November 2018 at Hong Kong meeting], He immediately drove back to Shenzhen, and his circle of trust began to disintegrate. He has not spoken publicly since. “I don’t think he can recover himself through PR,” says Ferrell, who no longer works for He but recently started to do part-time work for He’s wife. “He has to do other service to the world.”

Calls for a moratorium on human germline editing have increased, although at the end of the Hong Kong summit, the organizing committee declined in its consensus to call for a ban. China has stiffened its regulations on work with human embryos, and Chinese bioethicists in a Nature editorial about the incident urged the country to confront “the eugenic thinking that has persisted among a small proportion of Chinese scholars.”

Church, who has many CRISPR collaborations in China, finds it inconceivable that He’s work surprised the Chinese government. China has “the best surveillance system in the world,” he says. “I conclude that they were totally aware of what he was doing at every step of the way, especially because he wasn’t particularly secretive about it.”

Benjamin Hurlbut, William’s son and a historian of biomedicine at Arizona State University in Tempe, says leaders in the scientific community should take a hard look at their actions, too. [emphases mine] He thinks the 2017 NASEM report helped give rise to He by following a well-established approach to guiding science: appointing an elite group to decide how scientists should be regulated. Benjamin Hurlbut, whose book Experiments in Democracy explores the governance of embryo research and bioethics, questions why small, scientist-led groups—à la the totemic Asilomar conference held in 1975 to discuss the future of recombinant DNA research—are seen as the best way to shape thinking about new technologies. Hurlbut has called for a “global observatory for gene editing” to convene meetings with diverse perspectives.

The prevailing notion that the scientific community simply “failed to see the rogue among the responsible,” Hurlbut says, is a convenient narrative for those scientific leaders and inhibits their ability to learn from such failures. [emphases mine] “It puts them on the right side of history,” he says. They failed to paint a bright enough red line, Hurlbut contends. “They are not on the right side of history because they contributed to this.”

If you have the time, I strongly recommend reading Cohen’s piece in its entirety. You’ll find links to the reports and more articles with in-depth reporting on this topic.

A little kindness and no regrets

William Hurlbut was interviewed in an As it happens (Canadian Broadcasting Corporation’ CBC) radio programme segment on December 30, 2020. This is an excerpt from the story transcript written by Sheena Goodyear (Note: A link has been removed),

Dr. William Hurlbut, a physician and professor of neural-biology at Stanford University, says he tried to warn He to slow down before it was too late. Here is part of his conversation with As It Happens guest host Helen Mann.

What was your reaction to the news that Dr. He had been sentenced to three years in prison?

My first reaction was one of sadness because I know Dr. He — who we call J.K., that’s his nickname.

I spent quite a few hours talking with him, and I’m just sad that this worked out this way. It didn’t work out well for him or for his country or for the world, in some sense.

Except the one good thing is it’s alerted us, it’s awakened the world, to the seriousness of the issues that are coming down toward us with biotechnology, especially in genetics.

How does he feel about [how] not just the Chinese government, but the world generally, responded to his experiment?

He was surprised, personally. But I had actually warned him that he was proceeding too fast, and I didn’t know he had implanted embryos.

We had several conversations before this was disclosed, and I warned him to go more slowly and to keep in conversation with the rest of the international scientific community, and more broadly the international perspectives on social and ethical matters.

He was doing that to some extent, but not deeply enough and not transparently enough.

It sounds like you were very thoughtful in the conversations you had with him and the advice you gave him. And I guess you operated with what you had. But do you have any regrets yourself?

I don’t have any regrets about the way I conducted myself. I regret that this happened this way for J.K., who is a very bright person, and a very nice person, a humble person.

He grew up in a poor urban farming village. He told me that at one point he wanted to ask out a certain girl that he thought was really pretty … but he was embarrassed to do so because her family owned the restaurant. And so you see how humble his origins were.

By the way, he did end up asking her out and he ended up marrying her, which is a happy story, except now they’re separated for years of crucial time, and they have little children. 

I know this is a bigger story than just J.K. and his family. But there’s a personal story to it too.

What happens He Jiankui? … Is his research career over?

It’s hard to imagine that a nation like China would not give him some some useful role in their society. A very intelligent and very well-educated young man. 

But on the other hand, he will be forever a sign of a very crucial and difficult moment for the human species. He’s not going outlive that.

It’s going to be interesting. I hope I get a chance to have good conversations with him again and hear his internal ruminations and perspectives on it all.

This (“I don’t have any regrets about the way I conducted myself”) is where Hurlbut lost me. I think he could have suggested that he’d reviewed and rethought everything and feels that he and others could have done better and maybe they need to rethink how scientists are trained and how we talk about science, genetics, and emerging technology. Interestingly, it’s his son who comes up with something closer to what I’m suggesting (this excerpt was quoted earlier in this posting from a December 30, 2019 article, by Carolyn Y. Johnson for the Washington Post),

“The fact that the individual at the center of the story has been punished for his role in it should not distract us from examining what supporting roles were played by others, particularly in the international scientific community and also the environment that shaped and encouraged him to push the limits,” said Benjamin Hurlbut [emphasis mine], associate professor in the School of Life Sciences at Arizona State University.

The man who CRISPRs himself approves

Josiah Zayner publicly injected himself with CRISPR in a demonstration (see my January 25, 2018 posting for details about Zayner, his demonstration, and his plans). As you might expect, his take on the He affair is quite individual. From a January 2, 2020 article for STAT, Zayner presents the case for Dr. He’s work (Note: Links have been removed),

When I saw the news that He Jiankui and colleagues had been sentenced to three years in prison for the first human embryo gene editing and implantation experiments, all I could think was, “How will we look back at what they had done in 100 years?”

When the scientist described his research and revealed the births of gene edited twin girls at the [Second] International Summit on Human Genome Editing in Hong Kong in late November 2018, I stayed up into the early hours of the morning in Oakland, Calif., watching it. Afterward, I couldn’t sleep for a few days and couldn’t stop thinking about his achievement.

This was the first time a viable human embryo was edited and allowed to live past 14 days, much less the first time such an embryo was implanted and the baby brought to term.

The majority of scientists were outraged at the ethics of what had taken place, despite having very little information on what had actually occurred.

To me, no matter how abhorrent one views [sic] the research, it represents a substantial step forward in human embryo editing. Now there is a clear path forward that anyone can follow when before it had been only a dream.

As long as the children He Jiankui engineered haven’t been harmed by the experiment, he is just a scientist who forged some documents to convince medical doctors to implant gene-edited embryos. The 4-minute mile of human genetic engineering has been broken. It will happen again.

The academic establishment and federal funding regulations have made it easy to control the number of heretical scientists. We rarely if ever hear of individuals pushing the ethical and legal boundaries of science.

The rise of the biohacker is changing that.

A biohacker is a scientist who exists outside academia or an institution. By this definition, He Jiankui is a biohacker. I’m also part of this community, and helped build an organization to support it.

Such individuals have much more freedom than “traditional” scientists because scientific regulation in the U.S. is very much institutionally enforced by the universities, research organizations, or grant-giving agencies. But if you are your own institution and don’t require federal grants, who can police you? If you don’t tell anyone what you are doing, there is no way to stop you — especially since there is no government agency actively trying to stop people from editing embryos.

… When a human embryo being edited and implanted is no longer interesting enough for a news story, will we still view He Jiankui as a villain?

I don’t think we will. But even if we do, He Jiankui will be remembered and talked about more than any scientist of our day. Although that may seriously aggravate many scientists and bioethicists, I think he deserves that honor.

Josiah Zayner is CEO of The ODIN, a company that teaches people how to do genetic engineering in their homes.

You can find The ODIN here.

Final comments

There can’t be any question that this was inevitable. One needs only to take a brief stroll through the history of science to know that scientists are going to push boundaries or, as in this case, press past an ill-defined grey zone.

The only scientists who are being publicly punished for hubris are Dr. He Jiankui and his two colleagues in China. Dr. Michael Deem is still working for Rice University as far as I can determine. Here’s how the Wikipedia entry for the He Jiankui Affair describes the investigation (Note: Links have been removed),

Michael W. Deem, an American bioengineering professor at Rice University and He’s doctoral advisor, was involved in the research, and was present when people involved in He’s study gave consent.[24] He was the only non-Chinese out of 10 authors listed in the manuscript submitted to Nature.[30] Deem came under investigation by Rice University after news of the work was made public.[58] As of 31 December 2019, the university had not released a decision.[59] [emphasis mine]

Meanwhile the scientists at Stanford are cleared. While there are comments about the Chinese government not being transparent, it seems to me that US universities are just as opaque.

What seems missing from all this discussion and opprobrium is that the CRISPR technology itself is problematic. My September 20, 2019 post features research into off-target results from CRISPR gene-editing and, prior, there was this July 17, 2018 posting (The CRISPR [clustered regularly interspaced short palindromic repeats]-CAS9 gene-editing technique may cause new genetic damage kerfuffle).

I’d like to see more discussion and, in line with Benjamin Hurlbut’s thinking, I’d like to see more than a small group of experts talking to each other as part of the process especially here in Canada and in light of efforts to remove our ban on germline-editing (see my April 26, 2019 posting for more about those efforts).