Category Archives: human enhancement

Connecting biological and artificial neurons (in UK, Switzerland, & Italy) over the web

Caption: The virtual lab connecting Southampton, Zurich and Padova. Credit: University of Southampton

A February 26, 2020 University of Southampton press release (also on EurekAlert) describes this work,

Research on novel nanoelectronics devices led by the University of Southampton enabled brain neurons and artificial neurons to communicate with each other. This study has for the first time shown how three key emerging technologies can work together: brain-computer interfaces, artificial neural networks and advanced memory technologies (also known as memristors). The discovery opens the door to further significant developments in neural and artificial intelligence research.

Brain functions are made possible by circuits of spiking neurons, connected together by microscopic, but highly complex links called ‘synapses’. In this new study, published in the scientific journal Nature Scientific Reports, the scientists created a hybrid neural network where biological and artificial neurons in different parts of the world were able to communicate with each other over the internet through a hub of artificial synapses made using cutting-edge nanotechnology. This is the first time the three components have come together in a unified network.

During the study, researchers based at the University of Padova in Italy cultivated rat neurons in their laboratory, whilst partners from the University of Zurich and ETH Zurich created artificial neurons on Silicon microchips. The virtual laboratory was brought together via an elaborate setup controlling nanoelectronic synapses developed at the University of Southampton. These synaptic devices are known as memristors.

The Southampton based researchers captured spiking events being sent over the internet from the biological neurons in Italy and then distributed them to the memristive synapses. Responses were then sent onward to the artificial neurons in Zurich also in the form of spiking activity. The process simultaneously works in reverse too; from Zurich to Padova. Thus, artificial and biological neurons were able to communicate bidirectionally and in real time.

Themis Prodromakis, Professor of Nanotechnology and Director of the Centre for Electronics Frontiers at the University of Southampton said “One of the biggest challenges in conducting research of this kind and at this level has been integrating such distinct cutting edge technologies and specialist expertise that are not typically found under one roof. By creating a virtual lab we have been able to achieve this.”

The researchers now anticipate that their approach will ignite interest from a range of scientific disciplines and accelerate the pace of innovation and scientific advancement in the field of neural interfaces research. In particular, the ability to seamlessly connect disparate technologies across the globe is a step towards the democratisation of these technologies, removing a significant barrier to collaboration.

Professor Prodromakis added “We are very excited with this new development. On one side it sets the basis for a novel scenario that was never encountered during natural evolution, where biological and artificial neurons are linked together and communicate across global networks; laying the foundations for the Internet of Neuro-electronics. On the other hand, it brings new prospects to neuroprosthetic technologies, paving the way towards research into replacing dysfunctional parts of the brain with AI [artificial intelligence] chips.”

I’m fascinated by this work and after taking a look at the paper, I have to say, the paper is surprisingly accessible. In other words, I think I get the general picture. For example (from the Introduction to the paper; citation and link follow further down),

… To emulate plasticity, the memristor MR1 is operated as a two-terminal device through a control system that receives pre- and post-synaptic depolarisations from one silicon neuron (ANpre) and one biological neuron (BN), respectively. …

If I understand this properly, they’ve integrated a biological neuron and an artificial neuron in a single system across three countries.

For those who care to venture forth, here’s a link and a citation for the paper,

Memristive synapses connect brain and silicon spiking neurons by Alexantrou Serb, Andrea Corna, Richard George, Ali Khiat, Federico Rocchi, Marco Reato, Marta Maschietto, Christian Mayr, Giacomo Indiveri, Stefano Vassanelli & Themistoklis Prodromakis. Scientific Reports volume 10, Article number: 2590 (2020) DOI: https://doi.org/10.1038/s41598-020-58831-9 Published 25 February 2020

The paper is open access.

Humans with built-in night vision thanks to nanoparticles

In the world of video games such as the Deus Ex series eye augmentations are standard,now it seems that fantasy could become reality according to the latest American Chemical Society (ACS) meeting held in Fall 2019. From an August 27, 2019 news item on Nanowerk,

Movies featuring heroes with superpowers, such as flight, X-ray vision or extraordinary strength, are all the rage. But while these popular characters are mere flights of fancy, scientists have used nanoparticles to confer a real superpower on ordinary mice: the ability to see near-infrared light. Today, scientists report progress in making versions of these nanoparticles that could someday give built-in night vision to humans.

The researchers will present their results at the American Chemical Society (ACS) Fall 2019 National Meeting & Exposition.

“When we look at the universe, we see only visible light,” says Gang Han, Ph.D., the project’s principal investigator, who is presenting the work at the meeting. “But if we had near-infrared vision, we could see the universe in a whole new way. We might be able to do infrared astronomy with the naked eye, or have night vision without bulky equipment.”

An August 27, 2019 ACS news release, which originated the news item, explores the research about mammalian eyes (specifically mice) being presented in more depth,

The eyes of humans and other mammals can detect light between the wavelengths of 400 and 700 nanometers (nm). Near-infrared (NIR) light, on the other hand, has longer wavelengths — 750 nm to 1.4 micrometers. Thermal imaging cameras can help people see in the dark by detecting NIR radiation given off by organisms or objects, but these devices are typically bulky and inconvenient. Han and his colleagues wondered whether they could give mice NIR vision by injecting a special type of nanomaterial, called upconversion nanoparticles (UCNPs), into their eyes. These nanoparticles, which contain the rare-earth elements erbium and ytterbium, can convert low-energy photons from NIR light into higher-energy green light that mammalian eyes can see.

In work published earlier this year [2019], the researchers, who are at the University of Massachusetts Medical School, targeted UCNPs to photoreceptors in mouse eyes by attaching a protein that binds to a sugar molecule on the photoreceptor surface. Then, they injected the photoreceptor-binding UCNPs behind the retinas of the mice. To determine whether the injected mice could see and mentally process NIR light, the team conducted several physiological and behavioral tests. For example, in one test, the researchers placed the mice into a Y-shaped tank of water. One branch of the tank had a platform that the mice could climb on to escape the water. The researchers trained the mice to swim toward visible light in the shape of a triangle, which marked the escape route. A similarly lit circle marked the branch without a platform. Then, the researchers replaced the visible light with NIR light. “The mice with the particle injection could see the triangle clearly and swim to it each time, but the mice without the injection could not see or tell the difference between the two shapes,” says Han. A video of this work, posted by Han’s institution, can be viewed here.

Although the UCNPs persisted in the mice’s eyes for at least 10 weeks and did not cause any noticeable side effects, Han wants to improve the safety and sensitivity of the nanomaterials before he contemplates trying them out in humans. “The UCNPs in our published paper are inorganic, and there are some drawbacks there,” Han says. “The biocompatibility is not completely clear, and we need to improve the brightness of the nanoparticles for human use.” Now, the team is experimenting with UCNPs made up of two organic dyes, instead of rare-earth elements. “We’ve shown that we can make organic UCNPs with much improved brightness compared with the inorganic ones,” he says. These organic nanoparticles can emit either green or blue light. In addition to having improved properties, the organic dyes could also have fewer regulatory hurdles.

One of the next steps for the project might be translating the technology to man’s best friend. “If we had a super dog that could see NIR light, we could project a pattern onto a lawbreaker’s’ body from a distance, and the dog could catch them without disturbing other people,” Han says. Superhero powers aside, the technology could also have important medical applications, such as treating diseases of the eye. “We’re actually looking at how to use NIR light to release a drug from the UNCPs specifically at the photoreceptors,” Han says.

Here’s a link to and a citation for the paper mentioned in the ACS news release,

Mammalian Near-Infrared Image Vision through Injectable and Self-Powered Retinal Nanoantennae by Yuqian Ma, Jin Bao, Yuanwei Zhang, Zhanjun Li, Xiangyu Zhou. Changlin Wan, Ling Huang, Yang Zhao, Gang Han, Tian Xue. Cell Volume 177, ISSUE 2, P243-255.e15, April 04, 2019 DOI:https://doi.org/10.1016/j.cell.2019.01.038 First published online: February 28, 2019

This paper appears to be open access.

It’s going to be a while before this research makes it to human clinical trials, assuming it does. In the meantime, it seems that the plan is to continue research using dogs.

As you wait to find out how the researchers progress, you can check out my most recent mention of the Deus Ex video game series in a Sept. 1, 2016 posting about the latest entry to the series: Deus Ex: Mankind Divided.

An artificial graphene throat

A July 24, 2019 American Chemical Society (ACS) news release (received via email and also on EurekAlert) describes a ‘tattoo-like- artificial throat derived from graphene,

Most people take speech for granted, but it’s actually a complex process that involves both motions of the mouth and vibrations of folded tissues, called vocal cords, within the throat. If the vocal cords sustain injuries or other lesions, a person can lose the ability to speak. Now, researchers reporting in ACS Nano have developed a wearable artificial throat that, when attached to the neck like a temporary tattoo, can transform throat movements into sounds.

Scientists have developed detectors that measure movements on human skin, such as pulse or heartbeat. However, the devices typically can’t convert these motions into sounds. Recently, He Tian, Yi Yang, Tian-Ling Ren and colleagues developed a prototype artificial throat with both capabilities, but because the device needed to be taped to the skin, it wasn’t comfortable enough to wear for long periods of time. So the researchers wanted to develop a thinner, skin-like artificial throat that would adhere to the neck like a temporary tattoo.

To make their artificial throat, the researchers laser-scribed graphene on a thin sheet of polyvinyl alcohol film. The flexible device measured 0.6 by 1.2 inches, or about double the size of a person’s thumbnail. The researchers used water to attach the film to the skin over a volunteer’s throat and connected it with electrodes to a small armband that contained a circuit board, microcomputer, power amplifier and decoder. When the volunteer noiselessly imitated the throat motions of speech, the instrument converted these movements into emitted sounds, such as the words “OK” and “No.” The researchers say that, in the future, mute people could be trained to generate signals with their throats that the device would translate into speech.

Caption: A wearable artificial graphene throat, abbreviated here as ‘WAGT,’ can transform human throat movements into different sounds with training of the wearer. Credit: Adapted from ACS Nano 2019, 10.1021/acsnano.9b03218

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

A Wearable Skinlike Ultra-Sensitive Artificial Graphene Throat by Yuhong Wei, Yancong Qiao, Guangya Jiang, Yunfan Wang, Fangwei Wang, Mingrui Li, Yunfei Zhao, Ye Tian, Guangyang Gou, Songyao Tan He, Tian, Yi Yang, Tian-Ling Ren. ACS Nano2019XXXXXXXXXX-XXX DOI: https://doi.org/10.1021/acsnano.9b03218 Publication Date: July 3, 2019 Copyright © 2019 American Chemical Society

This paper is behind a paywall.

Touchy robots and prosthetics

I have briefly speculated about the importance of touch elsewhere (see my July 19, 2019 posting regarding BlocKit and blockchain; scroll down about 50% of the way) but this upcoming news bit and the one following it put a different spin on the importance of touch.

Exceptional sense of touch

Robots need a sense of touch to perform their tasks and a July 18, 2019 National University of Singapore press release (also on EurekAlert) announces work on an improved sense of touch,

Robots and prosthetic devices may soon have a sense of touch equivalent to, or better than, the human skin with the Asynchronous Coded Electronic Skin (ACES), an artificial nervous system developed by a team of researchers at the National University of Singapore (NUS).

The new electronic skin system achieved ultra-high responsiveness and robustness to damage, and can be paired with any kind of sensor skin layers to function effectively as an electronic skin.

The innovation, achieved by Assistant Professor Benjamin Tee and his team from the Department of Materials Science and Engineering at the NUS Faculty of Engineering, was first reported in prestigious scientific journal Science Robotics on 18 July 2019.

Faster than the human sensory nervous system

“Humans use our sense of touch to accomplish almost every daily task, such as picking up a cup of coffee or making a handshake. Without it, we will even lose our sense of balance when walking. Similarly, robots need to have a sense of touch in order to interact better with humans, but robots today still cannot feel objects very well,” explained Asst Prof Tee, who has been working on electronic skin technologies for over a decade in hope of giving robots and prosthetic devices a better sense of touch.

Drawing inspiration from the human sensory nervous system, the NUS team spent a year and a half developing a sensor system that could potentially perform better. While the ACES electronic nervous system detects signals like the human sensor nervous system, it is made up of a network of sensors connected via a single electrical conductor, unlike the nerve bundles in the human skin. It is also unlike existing electronic skins which have interlinked wiring systems that can make them sensitive to damage and difficult to scale up.

Elaborating on the inspiration, Asst Prof Tee, who also holds appointments in the NUS Department of Electrical and Computer Engineering, NUS Institute for Health Innovation & Technology (iHealthTech), N.1 Institute for Health and the Hybrid Integrated Flexible Electronic Systems (HiFES) programme, said, “The human sensory nervous system is extremely efficient, and it works all the time to the extent that we often take it for granted. It is also very robust to damage. Our sense of touch, for example, does not get affected when we suffer a cut. If we can mimic how our biological system works and make it even better, we can bring about tremendous advancements in the field of robotics where electronic skins are predominantly applied.”

ACES can detect touches more than 1,000 times faster than the human sensory nervous system. For example, it is capable of differentiating physical contacts between different sensors in less than 60 nanoseconds – the fastest ever achieved for an electronic skin technology – even with large numbers of sensors. ACES-enabled skin can also accurately identify the shape, texture and hardness of objects within 10 milliseconds, ten times faster than the blinking of an eye. This is enabled by the high fidelity and capture speed of the ACES system.

The ACES platform can also be designed to achieve high robustness to physical damage, an important property for electronic skins because they come into the frequent physical contact with the environment. Unlike the current system used to interconnect sensors in existing electronic skins, all the sensors in ACES can be connected to a common electrical conductor with each sensor operating independently. This allows ACES-enabled electronic skins to continue functioning as long as there is one connection between the sensor and the conductor, making them less vulnerable to damage.

Smart electronic skins for robots and prosthetics

ACES’ simple wiring system and remarkable responsiveness even with increasing numbers of sensors are key characteristics that will facilitate the scale-up of intelligent electronic skins for Artificial Intelligence (AI) applications in robots, prosthetic devices and other human machine interfaces.

“Scalability is a critical consideration as big pieces of high performing electronic skins are required to cover the relatively large surface areas of robots and prosthetic devices,” explained Asst Prof Tee. “ACES can be easily paired with any kind of sensor skin layers, for example, those designed to sense temperatures and humidity, to create high performance ACES-enabled electronic skin with an exceptional sense of touch that can be used for a wide range of purposes,” he added.

For instance, pairing ACES with the transparent, self-healing and water-resistant sensor skin layer also recently developed by Asst Prof Tee’s team, creates an electronic skin that can self-repair, like the human skin. This type of electronic skin can be used to develop more realistic prosthetic limbs that will help disabled individuals restore their sense of touch.

Other potential applications include developing more intelligent robots that can perform disaster recovery tasks or take over mundane operations such as packing of items in warehouses. The NUS team is therefore looking to further apply the ACES platform on advanced robots and prosthetic devices in the next phase of their research.

For those who like videos, the researchers have prepared this,

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

A neuro-inspired artificial peripheral nervous system for scalable electronic skins by Wang Wei Lee, Yu Jun Tan, Haicheng Yao, Si Li, Hian Hian See, Matthew Hon, Kian Ann Ng, Betty Xiong, John S. Ho and Benjamin C. K. Tee. Science Robotics Vol 4, Issue 32 31 July 2019 eaax2198 DOI: 10.1126/scirobotics.aax2198 Published online first: 17 Jul 2019:

This paper is behind a paywall.

Picking up a grape and holding his wife’s hand

This story comes from the Canadian Broadcasting Corporation (CBC) Radio with a six minute story embedded in the text, from a July 25, 2019 CBC Radio ‘As It Happens’ article by Sheena Goodyear,

The West Valley City, Utah, real estate agent [Keven Walgamott] lost his left hand in an electrical accident 17 years ago. Since then, he’s tried out a few different prosthetic limbs, but always found them too clunky and uncomfortable.

Then he decided to work with the University of Utah in 2016 to test out new prosthetic technology that mimics the sensation of human touch, allowing Walgamott to perform delicate tasks with precision — including shaking his wife’s hand. 

“I extended my left hand, she came and extended hers, and we were able to feel each other with the left hand for the first time in 13 years, and it was just a marvellous and wonderful experience,” Walgamott told As It Happens guest host Megan Williams. 

Walgamott, one of seven participants in the University of Utah study, was able to use an advanced prosthetic hand called the LUKE Arm to pick up an egg without cracking it, pluck a single grape from a bunch, hammer a nail, take a ring on and off his finger, fit a pillowcase over a pillow and more. 

While performing the tasks, Walgamott was able to actually feel the items he was holding and correctly gauge the amount of pressure he needed to exert — mimicking a process the human brain does automatically.

“I was able to feel something in each of my fingers,” he said. “What I feel, I guess the easiest way to explain it, is little electrical shocks.”

Those shocks — which he describes as a kind of a tingling sensation — intensify as he tightens his grip.

“Different variations of the intensity of the electricity as I move my fingers around and as I touch things,” he said. 

To make that [sense of touch] happen, the researchers implanted electrodes into the nerves on Walgamott’s forearm, allowing his brain to communicate with his prosthetic through a computer outside his body. That means he can move the hand just by thinking about it.

But those signals also work in reverse.

The team attached sensors to the hand of a LUKE Arm. Those sensors detect touch and positioning, and send that information to the electrodes so it can be interpreted by the brain.

For Walgamott, performing a series of menial tasks as a team of scientists recorded his progress was “fun to do.”

“I’d forgotten how well two hands work,” he said. “That was pretty cool.”

But it was also a huge relief from the phantom limb pain he has experienced since the accident, which he describes as a “burning sensation” in the place where his hand used to be.

A July 24, 2019 University of Utah news release (also on EurekAlert) provides more detail about the research,

Keven Walgamott had a good “feeling” about picking up the egg without crushing it.

What seems simple for nearly everyone else can be more of a Herculean task for Walgamott, who lost his left hand and part of his arm in an electrical accident 17 years ago. But he was testing out the prototype of a high-tech prosthetic arm with fingers that not only can move, they can move with his thoughts. And thanks to a biomedical engineering team at the University of Utah, he “felt” the egg well enough so his brain could tell the prosthetic hand not to squeeze too hard.

That’s because the team, led by U biomedical engineering associate professor Gregory Clark, has developed a way for the “LUKE Arm” (so named after the robotic hand that Luke Skywalker got in “The Empire Strikes Back”) to mimic the way a human hand feels objects by sending the appropriate signals to the brain. Their findings were published in a new paper co-authored by U biomedical engineering doctoral student Jacob George, former doctoral student David Kluger, Clark and other colleagues in the latest edition of the journal Science Robotics. A copy of the paper may be obtained by emailing robopak@aaas.org.

“We changed the way we are sending that information to the brain so that it matches the human body. And by matching the human body, we were able to see improved benefits,” George says. “We’re making more biologically realistic signals.”

That means an amputee wearing the prosthetic arm can sense the touch of something soft or hard, understand better how to pick it up and perform delicate tasks that would otherwise be impossible with a standard prosthetic with metal hooks or claws for hands.

“It almost put me to tears,” Walgamott says about using the LUKE Arm for the first time during clinical tests in 2017. “It was really amazing. I never thought I would be able to feel in that hand again.”

Walgamott, a real estate agent from West Valley City, Utah, and one of seven test subjects at the U, was able to pluck grapes without crushing them, pick up an egg without cracking it and hold his wife’s hand with a sensation in the fingers similar to that of an able-bodied person.

“One of the first things he wanted to do was put on his wedding ring. That’s hard to do with one hand,” says Clark. “It was very moving.”

Those things are accomplished through a complex series of mathematical calculations and modeling.

The LUKE Arm

The LUKE Arm has been in development for some 15 years. The arm itself is made of mostly metal motors and parts with a clear silicon “skin” over the hand. It is powered by an external battery and wired to a computer. It was developed by DEKA Research & Development Corp., a New Hampshire-based company founded by Segway inventor Dean Kamen.

Meanwhile, the U’s team has been developing a system that allows the prosthetic arm to tap into the wearer’s nerves, which are like biological wires that send signals to the arm to move. It does that thanks to an invention by U biomedical engineering Emeritus Distinguished Professor Richard A. Normann called the Utah Slanted Electrode Array. The array is a bundle of 100 microelectrodes and wires that are implanted into the amputee’s nerves in the forearm and connected to a computer outside the body. The array interprets the signals from the still-remaining arm nerves, and the computer translates them to digital signals that tell the arm to move.

But it also works the other way. To perform tasks such as picking up objects requires more than just the brain telling the hand to move. The prosthetic hand must also learn how to “feel” the object in order to know how much pressure to exert because you can’t figure that out just by looking at it.

First, the prosthetic arm has sensors in its hand that send signals to the nerves via the array to mimic the feeling the hand gets upon grabbing something. But equally important is how those signals are sent. It involves understanding how your brain deals with transitions in information when it first touches something. Upon first contact of an object, a burst of impulses runs up the nerves to the brain and then tapers off. Recreating this was a big step.

“Just providing sensation is a big deal, but the way you send that information is also critically important, and if you make it more biologically realistic, the brain will understand it better and the performance of this sensation will also be better,” says Clark.

To achieve that, Clark’s team used mathematical calculations along with recorded impulses from a primate’s arm to create an approximate model of how humans receive these different signal patterns. That model was then implemented into the LUKE Arm system.

Future research

In addition to creating a prototype of the LUKE Arm with a sense of touch, the overall team is already developing a version that is completely portable and does not need to be wired to a computer outside the body. Instead, everything would be connected wirelessly, giving the wearer complete freedom.

Clark says the Utah Slanted Electrode Array is also capable of sending signals to the brain for more than just the sense of touch, such as pain and temperature, though the paper primarily addresses touch. And while their work currently has only involved amputees who lost their extremities below the elbow, where the muscles to move the hand are located, Clark says their research could also be applied to those who lost their arms above the elbow.

Clark hopes that in 2020 or 2021, three test subjects will be able to take the arm home to use, pending federal regulatory approval.

The research involves a number of institutions including the U’s Department of Neurosurgery, Department of Physical Medicine and Rehabilitation and Department of Orthopedics, the University of Chicago’s Department of Organismal Biology and Anatomy, the Cleveland Clinic’s Department of Biomedical Engineering and Utah neurotechnology companies Ripple Neuro LLC and Blackrock Microsystems. The project is funded by the Defense Advanced Research Projects Agency and the National Science Foundation.

“This is an incredible interdisciplinary effort,” says Clark. “We could not have done this without the substantial efforts of everybody on that team.”

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

Biomimetic sensory feedback through peripheral nerve stimulation improves dexterous use of a bionic hand by J. A. George, D. T. Kluger, T. S. Davis, S. M. Wendelken, E. V. Okorokova, Q. He, C. C. Duncan, D. T. Hutchinson, Z. C. Thumser, D. T. Beckler, P. D. Marasco, S. J. Bensmaia and G. A. Clark. Science Robotics Vol. 4, Issue 32, eaax2352 31 July 2019 DOI: 10.1126/scirobotics.aax2352 Published online first: 24 Jul 2019

This paper is definitely behind a paywall.

The University of Utah researchers have produced a video highlighting their work,

Neural and technological inequalities

I’m always happy to see discussions about the social implications of new and emerging technologies. In this case, the discussion was held at the Fast Company (magazine) European Innovation Festival. KC Ifeanyi wrote a July 10, 2019 article for Fast Company highlighting a session between two scientists focusing on what I’ve termed ‘machine/flesh’ or is, sometimes, called a cyborg but not with these two scientists (Note: A link has been removed),

At the Fast Company European Innovation Festival today, scientists Moran Cerf and Riccardo Sabatini had a wide-ranging discussion on the implications of technology that can hack humanity. From ethical questions to looking toward human biology for solutions, here are some of the highlights:

The ethics of ‘neural inequality’

There are already chips that can be implanted in the brain to help recover bodily functions after a stroke or brain injury. However, what happens if (more likely when) a chip in your brain can be hacked or even gain internet access, essentially making it possible for some people (more likely wealthy people) to process information much more quickly than others?

“It’s what some call neural inequality,” says Cerf, a neuroscientist and business professor at the Kellogg School of Management and at the neuroscience program at Northwestern University. …

Opening new pathways to thought through bionics

Cerf mentioned a colleague who was born without his left hand. He engineered a bionic one that he can control with an app and that has the functionality of doing things no human hand can do, like rotating 360 degrees. As fun of a party trick as that is, Cerf brings up a good point in that his colleague’s brain is processing something we can’t, thereby possibly opening new pathways of thought.

“The interesting thing, and this is up to us to investigate, is his brain can think thoughts that you cannot think [emphasis mine] because he has a function you don’t have,” Cerf says. …

The innovation of your human body

As people look to advanced bionics to amplify their senses or abilities, Sabatini, chief data scientist at Orionis Biosciences, makes the argument that our biological bodies are far more advanced than we give them credit for. …

Democratizing tech’s edges

Early innovation so often comes with a high price tag. The cost of experimenting with nascent technology or running clinical trials can be exorbitant. And Sabatini believes democratizing that part of the process is where the true innovation will be. …

Earlier technology that changed our thinking and thoughts

This isn’t the first time that technology has altered our thinking and the kinds of thoughts we have as per ” brain can think thoughts that you cannot think.” According to Walter J. Ong’s 1982 book, ‘Orality and Literacy’,that’s what writing did to us; it changed our thinking and the kinds of thoughts we have.

It took me quite a while to understand ‘writing’ as a technology, largely due to how much I took it for granted. Once I made that leap, it changed how I understood the word technology. Then, the idea that ‘writing’ could change your brain didn’t require as dramatic a leap although it fundamentally altered my concept of the relationship between technology and humans. Up to that time, I had viewed technology as an instrument that allowed me to accomplish goals (e.g., driving a car from point a to point b) but it had very little impact on me as a person.

You can find out more about Walter J. Ong and his work in his Wikipedia entry. Pay special attention to the section about, Orality and Literacy.

Who’s talking about technology and our thinking?

The article about the scientists (Cerf and Sabatini) at the Fast Company European Innovation Festival (held July 9 -10, 2019 in Milan, Italy) never mentions cyborgs. Presumably, neither did Sabatini or Cerf. It seems odd. Two thinkers were discussing ‘neural inequality’ and there was no mention of a cyborg (human and machine joined together).

Interestingly, the lead sponsor for this innovation festival was Gucci. That company would not have been my first guess or any other guess for that matter as having an interest in neural inequality.

So, Gucci sponsored a festival that is not not cheap. A two-day pass was $1600. (early birds got a discount of $457) and a ‘super’ pass was $2,229 (with an early bird discount of $629). So, you didn’t get into the room unless you had a fair chunk of change and time.

The tension, talking about inequality at a festival or other venue that most people can’t afford to attend, is discussed at more length in Anand Giridharadas’s 2018 book, ‘Winners Take All; The Elite Charade of Changing the World’.

It’s not just who gets to discuss ‘neural inequality’, it’s when you get to discuss it, which affects how the discussion is framed.

There aren’t an easy answers to these questions but I find the easy assumption that the wealthy and the science and technology communities get first dibs at the discussion a little disconcerting while being perfectly predictable.

On the plus side, there are artists and others who have jumped in and started the discussion by turning themselves into cyborgs. This August 14, 2015 article (Body-hackers: the people who turn themselves into cyborgs) by Oliver Wainwright for the Guardian is very informative and not for the faint of heart.

For the curious, I’ve been covering these kinds of stories here since 2009. The category ‘human enhancement’ and the search term ‘machine/flesh’ should provide you with an assortment of stories on the topic.

Human-machine interfaces and ultra-small nanoprobes

We’re back on the cyborg trail or what I sometimes refer to as machine/flesh. A July 3, 2019 news item on ScienceDaily describes the latest attempts to join machine with flesh,

Machine enhanced humans — or cyborgs as they are known in science fiction — could be one step closer to becoming a reality, thanks to new research Lieber Group at Harvard University, as well as scientists from University of Surrey and Yonsei University.

Researchers have conquered the monumental task of manufacturing scalable nanoprobe arrays small enough to record the inner workings of human cardiac cells and primary neurons.

The ability to read electrical activities from cells is the foundation of many biomedical procedures, such as brain activity mapping and neural prosthetics. Developing new tools for intracellular electrophysiology (the electric current running within cells) that push the limits of what is physically possible (spatiotemporal resolution) while reducing invasiveness could provide a deeper understanding of electrogenic cells and their networks in tissues, as well as new directions for human-machine interfaces.

The Lieber Group at Harvard University provided this image illustrating the work,

U-shaped nanowires can record electrical chatter inside a brain or heart cell without causing any damage. The devices are 100 times smaller than their biggest competitors, which kill a cell after recording. Courtesy: University of Surrey

A July 3, 2019 University of Surrey press release (also on EurekAlert), which originated the news item, provides more details about this UK/US/China collaboration,

In a paper published by Nature Nanotechnology, scientists from Surrey’s Advanced Technology Institute (ATI) and Harvard University detail how they produced an array of the ultra-small U-shaped nanowire field-effect transistor probes for intracellular recording. This incredibly small structure was used to record, with great clarity, the inner activity of primary neurons and other electrogenic cells, and the device has the capacity for multi-channel recordings.

Dr Yunlong Zhao from the ATI at the University of Surrey said: “If our medical professionals are to continue to understand our physical condition better and help us live longer, it is important that we continue to push the boundaries of modern science in order to give them the best possible tools to do their jobs. For this to be possible, an intersection between humans and machines is inevitable.

“Our ultra-small, flexible, nanowire probes could be a very powerful tool as they can measure intracellular signals with amplitudes comparable with those measured with patch clamp techniques; with the advantage of the device being scalable, it causes less discomfort and no fatal damage to the cell (cytosol dilation). Through this work, we found clear evidence for how both size and curvature affect device internalisation and intracellular recording signal.”

Professor Charles Lieber from the Department of Chemistry and Chemical Biology at Harvard University said: “This work represents a major step towards tackling the general problem of integrating ‘synthesised’ nanoscale building blocks into chip and wafer scale arrays, and thereby allowing us to address the long-standing challenge of scalable intracellular recording.

“The beauty of science to many, ourselves included, is having such challenges to drive hypotheses and future work. In the longer term, we see these probe developments adding to our capabilities that ultimately drive advanced high-resolution brain-machine interfaces and perhaps eventually bringing cyborgs to reality.”

Professor Ravi Silva, Director of the ATI at the University of Surrey, said: “This incredibly exciting and ambitious piece of work illustrates the value of academic collaboration. Along with the possibility of upgrading the tools we use to monitor cells, this work has laid the foundations for machine and human interfaces that could improve lives across the world.”

Dr Yunlong Zhao and his team are currently working on novel energy storage devices, electrochemical probing, bioelectronic devices, sensors and 3D soft electronic systems. Undergraduate, graduate and postdoc students with backgrounds in energy storage, electrochemistry, nanofabrication, bioelectronics, tissue engineering are very welcome to contact Dr Zhao to explore the opportunities further.

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

Scalable ultrasmall three-dimensional nanowire transistor probes for intracellular recording by Yunlong Zhao, Siheng Sean You, Anqi Zhang, Jae-Hyun Lee, Jinlin Huang & Charles M. Lieber. Nature Nanotechnology (2019) DOI: https://doi.org/10.1038/s41565-019-0478-y Published 01 July 2019

The link I’ve provided leads to a paywall. However, I found a freely accessible version of the paper (this may not be the final published version) here.

Ethics of germline editing special CRISPR journal issue

Caption: The CRISPR Journal delivers groundbreaking multidisciplinary research, advances, and commentary on CRISPR, the extraordinary technology that gives scientists the power to cure disease and sculpt evolution. Credit: Mary Ann Liebert, Inc., publishers

The CRISPR Journal’s publisher, Mary Ann Liebert, Inc., released two notices about their special issue on ethics. I found this October 10, 2019 media alert on EurekAlert a little more informative than the other one,

Highlights from this Issue:

1. Human Germline Genome Editing: An Assessment
In the opening Perspective of the special issue on The Ethics of Human Genome Editing, Stanford Law professor Henry Greely argues that germline editing is not inherently bad or unethical, but the technology is unlikely to be particularly useful, at least in the near future. Greely takes issue with the notion that the human genome is “the heritage of humanity” – the equivalent of The Ark of the Covenant that “cannot be allowed to fall into the wrong hands.” He contrasts germline editing with the practical applications of preimplantation genetic testing and somatic gene therapy. Exceptions for germline editing might be found in the cases of rare couples where both partners have the same recessive disorder or one is homozygous for a dominant disease.

2. Pick Six: Democratic Governance of Germline Editing
Two international commissions, organized by the World Health Organization, the U.S. National Academies, and the Royal Society, have been launched to provide recommendations for the governance of human germline editing, prompted by the actions of He Jiankui and the 2018 CRISPR babies reports. In this Perspective, Jasanoff, Hurlbut, and Saha [Sheila Jasanoff, Harvard University {Cambridge, MA}, J. Benjamin Hurlbut, Arizona State University {Tempe, AZ}, and Krishanu Saha, University of Wisconsin-Madison] argue that such an approach is “premature and problematic.” Global democratic governance “demands a new mechanism for active, sustained reflection by scientists” in partnership with scholars from other disciplines and the public. The authors present six recommendations to promote democratic governance.

3. Just Say No to a Moratorium
In March 2019, Eric Lander, Francoise Baylis [emphasis mine], and colleagues issued a call for a temporary global moratorium on heritable genome editing. In this Perspective, Kerry Macintosh, author of Enhanced Beings, offers three reasons she opposes the imposition of a moratorium: the danger of a temporary ban becoming permanent; a disincentive to support appropriate research to make the technology safer and more effective; and the potential stigmatization of children born with edited genomes. Nations should regulate germline editing for safety and efficacy only, Macintosh says, without distinguishing between therapeutic applications and enhancement.

4. Who Speaks for Future Children?
Law professor Bartha Knoppers and Erika Kleiderman write that the recent calls for a moratorium on germline editing “may create an illusion of control over rogue science and stifle the necessary international debate surrounding an ethically responsible translational path forward.” Focusing efforts on enforcing current laws and fostering public dialogue is a better route, the authors suggest.

5. The Daunting Economics of Therapeutic Genome Editing
Ten years after the first gene editing clinical trial got underway, gene therapy is experiencing a renaissance. Recent approvals for some gene therapy drugs have been accompanied by exorbitant price tags, in one case exceeding $2 million. Looking ahead, Wilson [Ross C. Wilson, PhD, Innovative Genomics Institute, University of California, Berkeley] and Carroll [Dana Carroll, PhD, Department of Biochemistry, University of Utah School of Medicine] ask whether CRISPR can make good on its promise as “a great leveler” and “democratizing force in biomedicine”. They write: “Therapeutic genome editing must avoid several pitfalls that could substantially limit access to its transformative potential, especially in the developing world.” The costs of drug manufacture, testing, and delivery will have to come down to make the benefits of genome editing available to those most in need.

6. The Demand for Germline Editing: View from a Fertility Clinic
A common argument against human germline editing is that there is already a safe, proven technology to help couples have a healthy biological child — preimplantation genetic testing (PGT). In this Perspective, Manuel Viotti and colleagues from a leading IVF clinic in California strive to calculate the likely occurrence of cases where germline editing might offer couples opportunities to have a healthy biological child where PGT would not be applicable. The numbers are very small indeed.

7. Brave New World in the CRISPR Debate
In any discussion or warnings of designer babies and future dystopian societies based on genetic or reproductive technologies, exhibit A is invariably Aldous Huxley’s iconic 1932 novel, Brave New World. Indeed, David Baltimore referred to the novel at both of the international genome editing summits. In this Perspective, Derek So dissects the misuse of Brave New World, particularly regarding genome editing technology, enhancement, and eugenics. So [even offers a few less celebrated, but potentially more appropriate, examples from the sci-fi literature.

I highlighted Françoise Baylis’ name as she has been mentioned on this blog a few times and, if you’re curious, there’s an opportunity to hear her speak in Toronto (Ontario) tonight, Thursday, October 17, 2019. You can find out where and exactly when in my October 14, 2019 posting, under the first subheading, ‘… on the future of life forms …’.

The October 15, 2019 news release on EurekAlert offers much the same information but also includes this link to the journal issue where you can read it for free,

The Ethics of Human Genome Editing is the subject of intensive discussion and debate in a special issue of The CRISPR Journal, a new peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here) to read the full-text issue free on The CRISPR Journal.

The issue contains 11 articles: nine Perspectives and two research articles on issues including human rights for the unborn, the economics of gene editing therapies, the pros and cons of a moratorium on genome editing, the real-world cases where germline editing could provide medical utility, and (on a lighter note) the use and misuse of “Brave New World.”

It looks like a very interesting and comprehensive lineup of topics related to ethics and editing the human germline. FYI, I covered the story about the CRISPR twins, Lulu and Nana, here in a November 28, 2018 posting, about the time the news first broke.

Detecting off-target effects of CRISPR gene-editing

In amidst all the hyperbole about CRISPR (clustered regularly interspaced short palindromic repeats), the gene editing technology, you will sometimes find a mild cautionary note. It seems that CRISPR is not as precise as you might think.

Some months ago there was a story about research into detecting possible unanticipated (off target) effects from using CRISPR, from an April 19, 2019 news item on ScienceDaily,

Since the CRISPR genome editing technology was invented in 2012, it has shown great promise to treat a number of intractable diseases. However, scientists have struggled to identify potential off-target effects in therapeutically relevant cell types, which remains the main barrier to moving therapies to the clinic. Now, a group of scientists at the Gladstone Institutes and the Innovative Genomics Institute (IGI), with collaborators at AstraZeneca, have developed a reliable method to do just that.

An April 19, 2019 Gladstone Institutes press release by Julie Langelier, which originated the press release, provides details,

CRISPR edits a person’s genome by cutting the DNA at a specific location. The challenge is to ensure the tool doesn’t also make cuts elsewhere along the DNA—damage referred to as “off-target effects,” which could have unforeseen consequences.

In a study published in the journal Science, the two first authors, Beeke Wienert and Stacia Wyman, found a new way to approach the problem.

“When CRISPR makes a cut, the DNA is broken,” says Wienert, PhD, who began the work in Jacob E. Corn’s IGI laboratory and who is now a postdoctoral scholar in Bruce R. Conklin’s laboratory at Gladstone. “So, in order to survive, the cell recruits many different DNA repair factors to that particular site in the genome to fix the break and join the cut ends back together. We thought that if we could find the locations of these DNA repair factors, we could identify the sites that have been cut by CRISPR.”

To test their idea, the researchers studied a panel of different DNA repair factors. They found that one of them, called MRE11, is one of the first responders to the site of the cut. Using MRE11, the scientists developed a new technique, named DISCOVER-Seq, that can identify the exact sites in the genome where a cut has been made by CRISPR.

“The human genome is extremely large—if you printed the entire DNA sequence, you would end up with a novel as tall as a 16-story building,” explains Conklin, MD, senior investigator at Gladstone and deputy director at IGI. “When we want to cut DNA with CRISPR, it’s like we’re trying to remove one specific word on a particular page in that novel.”

“You can think of the DNA repair factors as different types of bookmarks added to the book,” Conklin adds. “While some may bookmark an entire chapter, MRE11 is a bookmark that drills down to the exact letter than has been changed.”

Different methods currently exist to detect CRISPR off-target effects. However, they come with limitations that range from producing false-positive results to killing the cells they’re examining. In addition, the most common method used to date is currently limited to cultured cells in the laboratory, excluding its use in patient-derived stem cells or animal tissue.

“Because our method relies on the cell’s natural repair process to identify cuts, it has proven to be much less invasive and much more reliable,” says Corn, PhD, who now runs a laboratory at ETH Zurich. “We were able to test our new DISCOVER-Seq method in induced pluripotent stem cells, patient cells, and mice, and our findings indicate that this method could potentially be used in any system, rather than just in the lab.”

The DISCOVER-Seq method, by being applied to new cell types and systems, has also revealed new insights into the mechanisms used by CRISPR to edit the genome, which will lead to a better understanding of the biology of how this tool works.

“The new method greatly simplifies the process of identifying off-target effects while also increasing the accuracy of the results,” says Conklin, who is also a professor of medical genetics and molecular pharmacology at UC San Francisco (UCSF). “This could allow us to better predict how genome editing would work in a clinical setting. As a result, it represents an essential step in improving pre-clinical studies and bringing CRISPR-based therapies closer to the patients in need.”

###

About the Study

The paper “Unbiased detection of CRISPR off-targets in vivo 1 using DISCOVER-Seq” was published by the journal Science on April 19, 2019. Gladstone’s Hannah L. Watry and Luke M. Judge (who is also at UCSF) contributed to this study. Other authors also include Christopher D. Richardson, Jonathan T. Vu, and Katelynn R. Kazane from IGI, Charles D. Yeh from ETH Zurich, as well as Pinar Akcakaya, Michelle J. Porritt, and Michaela Morlock from AstraZeneca.

The work was supported by Gladstone, the National Institutes of Health (grants EY028249 and HL13535801), the Li Ka Shing Foundation, the Heritage Medical Research Institute, the Fanconi Anemia Research Foundation, a Sir Keith Murdoch Fellowship from the American Australian Association, and an Early Career Fellowship from the National Health and Medical Research Council.

About the Gladstone Institute

To ensure our work does the greatest good, the Gladstone Institutes focuses on conditions with profound medical, economic, and social impact—unsolved diseases. Gladstone is an independent, nonprofit life science research organization that uses visionary science and technology to overcome disease. It has an academic affiliation with the University of California, San Francisco.

Before getting to the link and citation that I usually offer you might find this July 17, 2018 posting, The CRISPR ((clustered regularly interspaced short palindromic repeats)-CAS9 gene-editing technique may cause new genetic damage kerfuffle of interest. I wonder if this latest news affected the CRISPR market as the did the news in 2018.

In addition to the link in the press release, I am including a link and a citation for the study,

Unbiased detection of CRISPR off-targets in vivo using DISCOVER-Seq by Beeke Wienert, Stacia K. Wyman, Christopher D. Richardson, Charles D. Yeh, Pinar Akcakaya, Michelle J. Porritt, Michaela Morlock, Jonathan T. Vu, Katelynn R. Kazane, Hannah L. Watry, Luke M. Judge, Bruce R. Conklin, Marcello Maresca, Jacob E. Corn. Science 19 Apr 2019: Vol. 364, Issue 6437, pp. 286-289 DOI: 10.1126/science.aav9023

This paper is behind a paywall.

Money

Over the last 10 or more years, I have, on occasion made a point, of finding out about the funding for various non-profit agencies and projects. I find that sort of thing interesting and have hoped that my readers might feel the same way.

It seems that my readers and I might not be the only ones to care about the source of funding. Joi Ito who held appointments with Harvard University and the Massachusetts Institute of Technology (MIT) resigned from his various appointments on Sept. 7, 2019 after news of major donations from Jeffrey Epstein (a disgraced financier and sex offender) to MIT were revealed. From the Joi Ito’s entry on Wikipedia (Note: Links have been removed),

Joichi “Joi” Ito (伊藤 穰一 Itō Jōichi, born June 19, 1966) is a Japanese activist, entrepreneur and venture capitalist. He is the former director of the MIT Media Lab, and a former professor of the practice of media arts and sciences at MIT. He is a former visiting professor of practice at the Harvard Law School.[1][2]

Ito has received recognition for his role as an entrepreneur focused on Internet and technology companies and has founded, among other companies, PSINet Japan, Digital Garage and Infoseek Japan. Ito is a strategic advisor to Sony Corporation[3] and general partner of Neoteny Labs.[4] Ito writes a monthly column in the Ideas section of Wired.[5]

Ito resigned from his roles at MIT, Harvard, the John D. and Catherine T. MacArthur Foundation, the Knight Foundation, PureTech Health and The New York Times Company on September 7, 2019, following allegations of financial ties to sex offender and financier Jeffrey Epstein.[2][6][7]

Many, many institutions have accepted funds from sketchy characters and orgnaizations. It’s not new to academia, the sciences, or the arts. For a contemporary view of how some of this works, take a look at Anand Giridharadas’s 2018 book, Winners Take All. From the webepage for the book,

WINNERS TAKE ALL
The Elite Charade of Changing the World
 
An insider’s groundbreaking investigation of how the global elite’s efforts to “change the world” preserve the status quo and obscure their role in causing the problems they later seek to solve.

Former New York Times columnist Anand Giridharadas takes us into the inner sanctums of a new gilded age, where the rich and powerful fight for equality and justice any way they can–except ways that threaten the social order and their position atop it. We see how they rebrand themselves as saviors of the poor; how they lavishly reward “thought leaders” who redefine “change” in winner-friendly ways; and how they constantly seek to do more good, but never less harm. We hear the limousine confessions of a celebrated foundation boss; witness an American president hem and haw about his plutocratic benefactors; and attend a cruise-ship conference where entrepreneurs celebrate their own self-interested magnanimity.

I don’t recall any mention of Epstein in Giridharadas’s book but he did have this to say on Twitter about Epstein,

Anand Giridharadas‏Verified account @AnandWrites



Everything that made Epstein’s life possible remains in place after his arrest: the Caribbean tax havens, the hidden real-estate deals, the buying of politicians, the nonprofits that sell reputational glow, the editors who cover for people of their class.

7:34 PM – 8 Jul 2019

it can’t be easy to withstand the temptation to take the money and hope that the misdoings have been exaggerated or that they have stopped. I imagine Ito and others are under constant pressure to get funds.

AstraZeneca

One of the partners in this research about CRISPR, AstraZeneca, is a pharmaceutical company. In fact, it’s one of the largest in the world (from the AstraZeneca Wikipedia entry; Note: Links have been removed),

AstraZeneca plc[4] is a British-Swedish multinational pharmaceutical and biopharmaceutical company. In 2013, it moved its headquarters to Cambridge, UK, and concentrated its R&D in three sites: Cambridge; Gaithersburg, Maryland, USA (location of MedImmune) for work on biopharmaceuticals; and Mölndal (near Gothenburg) in Sweden, for research on traditional chemical drugs.[5] AstraZeneca has a portfolio of products for major disease areas including cancer, cardiovascular, gastrointestinal, infection, neuroscience, respiratory and inflammation.[6]

The company was founded in 1999 through the merger of the Swedish Astra AB and the British Zeneca Group[7][8] (itself formed by the demerger of the pharmaceutical operations of Imperial Chemical Industries in 1993). Since the merger it has been among the world’s largest pharmaceutical companies and has made numerous corporate acquisitions, including Cambridge Antibody Technology (in 2006), MedImmune (in 2007), Spirogen (in 2013) and Definiens (by MedImmune in 2014).

Controversies

Seroquel
In April 2010 AstraZeneca settled a qui tam lawsuit brought by Stefan P. Kruszewski for $520 million to settle allegations that the company defrauded Medicare, Medicaid, and other government-funded health care programs in connection with its marketing and promotional practices for the blockbuster atypical antipsychotic, Seroquel.[76]
In March 2011, AstraZeneca settled a lawsuit in the United States totalling $68.5 million to be divided up to 38 states.[77]
Nexium
The company’s most commercially successful medication is esomeprazole (Nexium). The primary uses are treatment of gastroesophageal reflux disease, treatment and maintenance of erosive esophagitis, treatment of duodenal ulcers caused by Helicobacter pylori, prevention of gastric ulcers in those on chronic NSAID therapy, and treatment of gastrointestinal ulcers associated with Crohn’s disease. When it is manufactured the result is a mixture of two mirror-imaged molecules, R and S. Two years before the omeprazole patent expired, AstraZeneca patented S-omeprazole in pure form, pointing out that since some people metabolise R-omeprazole slowly, pure S-omeprazole treatment would give higher dose efficiency and less variation between individuals.[78] In March 2001, the company began to market Nexium, as it would a brand new drug.[79]

In 2007, Marcia Angell, former editor-in-chief of the New England Journal of Medicine and a lecturer in social medicine at the Harvard Medical School, said in Stern, a German-language weekly newsmagazine, that AstraZeneca’s scientists had misrepresented their research on the drug’s efficiency, saying “Instead of using presumably comparable doses [of each drug], the company’s scientists used Nexium in higher dosages. They compared 20 and 40 mg Nexium with 20 mg Prilosec. With the cards having been marked in that way, Nexium looked like an improvement – which however was only small and shown in only two of the three studies.”[83]
Bildman fraud, and faithless servant clawback

Study
In 2004, University of Minnesota research participant Dan Markingson committed suicide while enrolled in an industry-sponsored pharmaceutical trial comparing three FDA-approved atypical antipsychotics: Seroquel (quetiapine), Zyprexa (olanzapine), and Risperdal (risperidone). University of Minnesota Professor of Bioethics Carl Elliott noted that Markingson was enrolled in the study against the wishes of his mother, Mary Weiss, and that he was forced to choose between enrolling in the study or being involuntarily committed to a state mental institution.[89] Further investigation revealed financial ties to AstraZeneca by Markingson’s psychiatrist, Stephen C. Olson, oversights and biases in AstraZeneca’s trial design, and the inadequacy of university Institutional Review Board (IRB) protections for research subjects.[90][unreliable source?] A 2005 FDA investigation cleared the university. Nonetheless, controversy around the case has continued. A Mother Jones article[89] resulted in a group of university faculty members sending a public letter to the university Board of Regents urging an external investigation into Markingson’s death.[91]

Is it ok to take money and/or other goods and services from them?

Innovative Genomics Institute (IGI)

Also mentioned as a partner in the research, is the Innovative Genomics Institute (IGI). Here’s more from the company’s Overview webpage (Note: Links have been removed),,

The IGI began in 2014 through the Li Ka Shing Center for Genetic Engineering, which was created thanks to a generous donation from the Li Ka Shing Foundation. [emphasis mine] The Innovative Genomics Initiative formed as a partnership between the University of California, Berkeley and the University of California, San Francisco. Combining the fundamental research expertise and the biomedical talent at UCB and UCSF, the Innovative Genomics Initiative focused on unraveling the mechanisms underlying CRISPR-based genome editing and applying this technology to improve human health. Early achievements include improving the efficiency of gene replacement and foundational work toward a treatment for sickle cell disease.

In late 2015, generous philanthropic donations enabled a bolder vision and broader mission for the IGI. With this expansion came a significant enhancement of the organization, and in January 2017, the IGI officially re-launched as the Innovative Genomics Institute.

As it turns out, there is a Li Ka-shing and he has a bit of a history with Vancouver (Canada). First, here’s more about him from the Li Ka-shing Wikipedia entry,(Note: Links have been removed),

Sir Li Ka-shing GBM KBE JP[4] (born 13 June 1928)[5][6] is a Hong Kong business magnate, investor, and philanthropist. As of June 2019, Li is the 30th richest person in the world, with an estimated net wealth of US$29.4 billion.[3] He is the senior advisor for CK Hutchison Holdings,[7] after he retired from the Chairman of the Board in May 2018;[8] through it, he is the world’s leading port investor, developer, and operator of the largest health and beauty retailer in Asia and Europe.[9]

Besides business through his flagship companies Cheung Kong Property Holdings and CK Hutchison Holdings Limited, Li Ka-shing has also personally invested extensively in real estate in Singapore and Canada. He was the single largest shareholder of Canadian Imperial Bank of Commerce (CIBC), the fifth largest bank in Canada, until the sale of his share in 2005 (with all proceedings donated, see below). He is also the majority shareholder of a major energy company, Husky Energy, based in Alberta, Canada.[48]

In January 2005, Li announced plans to sell his $1.2 billion CAD stake in the Canadian Imperial Bank of Commerce, with all proceeds going to private charitable foundations established by Li, including the Li Ka Shing Foundation in Hong Kong and the Li Ka Shing (Canada) Foundation based in Toronto, Ontario.[49]

His son Victor Li was kidnapped in 1996 on his way home after work by gangster “Big Spender” Cheung Tze-keung. Li Ka-shing paid a ransom of HK$1 billion, directly to Cheung who had come to his house.[53] A report was never filed with Hong Kong police. Instead the case was pursued by Mainland authorities, leading to Cheung’s execution in 1998, an outcome not possible under Hong Kong law. Rumours circulated of a deal between Li and the Mainland.[53] In interviews, when this rumor was brought up, Li brushed it off and dismissed it completely.

Li Ka-shing was well known here in Vancouver due to his purchase of a significant chunk of land in the city. This January 9, 2015 article by Glen Korstrum for Business in Vancouver notes some rather interesting news and contextualizes with Li’s Vancouver history,

Hong Kong billionaire Li Ka-shing is restructuring his empire and shifting his base to the Cayman Islands and away from the Chinese special administrative region.

His January 9 [2015] announcement came the same day that Forbes ranked him as Hong Kong’s richest man for the 17th consecutive year, with a total wealth of US$33.5 billion.

Li is best known in Vancouver for buying an 82.5-hectare parcel of land around False Creek for $328 million in 1988 along with partners, who included fellow Hong Kong tycoons, Lee Shau Kee and Cheng Yu Tung.

The group formed Concord Pacific, which redeveloped the site that had been home to Vancouver’s 1986 world’s fair, Expo ’86.

Li cashed out of Concord Pacific in the late 1990s and, in 2007, invested in Deltaport through his Hutchison Port Holdings.

Li’s biggest Canadian holding is his controlling stake in Husky Energy. …

Intriguing, yes? It also makes the prospect of deciding whose money you’re going to accept a bit more complicated than it might seem.

Gladstone Institutes

In what seems to be a decided contrast to the previous two partners, here’s more from the Gladstone Institutes, About Us, History webpage,

Born in London in 1910, J. David Gladstone was orphaned as a boy and came to North America at age 10. He began a career in real estate in Southern California at age 28, eventually making his fortune as the first developer to create the region’s enclosed shopping malls (such as the Northridge Fashion Center mall). His accidental death in 1971 left an estate valued at about $8 million to support medical students interested in research.

It soon became clear to the three trustees administering Mr. Gladstone’s trust that his legacy could support a far more substantial philanthropic enterprise. In 1979, they launched The J. David Gladstone Institutes under the leadership of Robert W. Mahley, MD, PhD, a leading cardiovascular scientist who at the time was working at the National Institutes of Health.

In 2010, after three decades of leading Gladstone, Dr. Mahley stepped down in order to return to more active research. That same year, R. Sanders “Sandy” Williams, MD, left Duke University, where he had been Dean of the School of Medicine—as well as Senior Vice Chancellor and Senior Advisor for International Strategy—to become Gladstone’s new president. The following year, the S.D. Bechtel, Jr. Foundation [emphasis mine] helped launch the Center for Comprehensive Alzheimer’s Disease Research with a generous $6M lead gift, while the Roddenberry Foundation [emphasis mine] gave $5 million to launch the Roddenberry Center for Stem Cell Biology and Medicine. Also in 2011, the independent and philanthropic Gladstone Foundation formed with the mission of expanding the financial resources available to drive’s Gladstone’s mission.

The S. D. Bechtel jr. mentioned is associated with Bechtel, an international engineering firm. I did not find any scandals or controversies in the Bechtel Wikipedia entry. That seemed improbable so I did a little digging and found a January 30, 2015 (?) article by Matthew Brunwasser for foreignpolicy.com (Note: A link has been removed),

Steamrolled; A special investigation into the diplomacy of doing business abroad.

One of Europe’s poorest countries wanted a road, so U.S. mega-contractor Bechtel sold it a $1.3 billion highway, with the backing of a powerful American ambassador. Funny thing is, the highway is barely being used—and the ambassador is now working for Bechtel.

Bechtel, the largest contractor by revenue in the United States and the third-largest internationally, according to an annual list compiled by the Engineering News-Record, has in recent years constructed expensive highways in Kosovo, Croatia, Romania, and Albania. A six-month investigation by the Investigative Reporting Program at the University of California at Berkeley Graduate School of Journalism has found that these highways were boondoggles for the countries in which they were constructed, and that members of governments and international institutions often saw problems coming before Bechtel (along with its Turkish joint venture partner, Enka) even began work on the roads.

My other source is a May 8, 1988 article by Walter Russell Mead for the Los Angeles Time,s

From San Francisco to Saudi Arabia, the Bechtel Group Inc. has left its mark around the world. Yet the privately owned Bechtel Group is one of the country’s most mysterious operations–or was, until the publication of Laton McCartney’s critical and controversial “Friends in High Places.”

Those who believe that “Dynasty” and “Falcon Crest” describe life at the top of America’s corporate pyramids will find a picture here that makes the most far-fetched TV plots look dull. One Bechtel executive was torn to pieces by an angry mob; another, kidnaped, survived two days in the trunk of a Mercedes that had been driven over the edge of a cliff but caught on an obstacle half way down. Wheeling and dealing from Beirut to the Bohemian Grove, Bechtel executives fought off Arab and Jewish nationalists, angry senators, bitter business rivals, and furious consumer groups to build the world’s largest construction and engineering firm.

Poor Bechtel sometimes seems damned if it does and damned if it doesn’t. No major corporation could undertake foreign operations on Bechtel’s scale without some cooperation from the U.S. government–and few companies could refuse a government request that, in return, they provide cover for intelligence agents. Given the enormous scope of Bechtel’s operations in global trouble spots–a $20-billion industrial development in Saudi Arabia, for example–it could only proceed with assurances that its relations with both Saudi and American governments were good. Where, exactly, is the line between right and wrong? [emphasis mine]

… The white elephants Bechtel scattered across the American landscape–particularly the nuclear power plants that threaten to bankrupt some of the country’s largest utility systems–are monuments to wasted talent and misdirected resources.

Finally, I get to the Roddenberry Foundation, which was founded by Gene Roddenberry’s (Star Trek) son. Here’s more from the About Us, Origin webpage,

Gene Roddenberry, creator of the Star Trek series, brought to his audiences meaningful and thought-provoking science fiction to “think, question, and challenge the status quo” with the intention of creating “a brighter future”. His work has touched countless lives and continues to entertain and inspire audiences worldwide. In 2010, Gene’s son Rod established the Roddenberry Foundation to build on his father’s legacy and philosophy of inclusion, diversity, and respect for life to drive social change and meaningfully improve the lives of people around the world.

While there are many criticisms of Mr. Roddenberry, there doesn’t seem to be anything that would be considered a serious scandal on the order of a Jeffrey Epstein or the whisper of scandal on the order of Sir Li Ka-shing or Bechtel.

Final comments

It’s a good thing when research is funded and being able to detect off-target effects from CRISPR is very good, assuming the research holds up to closer scrutiny.

As for vetting your donors, that’s tricky. Of course, Epstein was already a convicted sex offender when Ito accepted his funding for MIT but I cannot emphasize enough the amount of pressure these folks are under. Academia is always hungry for money. Hopefully this incident will introduce checks and balances in the donor process.

Needle-free tattoos, smart and otherwise

Before getting to the research news from the University of Twente (Netherlands), there’s this related event which took place on April 18, 2019 (from the Future Under Our Skin webpage (on the University of Twente website) Note: I have made some formatting changes,

Why this event?

Our skin can give information about our health, mood and surroundings. Medical and recreational tattoos have decorated humans for centuries. But we can inject other materials besides ink, such as sensing devices, nano- or bio-responsive materials. With the increased percentage of tattooed population in recent years new health challenges have emerged; but is also a unique possibility to “read from our own skin”, beyond an artistic design. 
 
We have invited scientists, innovators, entrepreneurs, dermatologists, cosmetic permanent make-up technicians, tattoo artists, philosophers, and other experts. They will share with us their vision of the current and future role our skin has for improving the quality of life.

Open Event

This event is open to students, citizens in general as well as societal and governmental organisations around the different uses of our skin. The presence of scientists, medical doctors, tattoo artists and industry representatives is guaranteed. Then, we will all explore together the potential for co-creation with healthy citizens, patients, entreprises and other stakeholders.


If you want to hear from experts and share your own ideas, feel free to come to this Open Event!
 
It is possible to take the dish of the day (‘goed gevulde noedels met kippendij en satésaus en kroepoek’) in restaurant The Gallery (same building as DesignLab) at own costs (€7,85). Of course it is also possible to eat à la carte in Grand Café 

Wanneer: : 18 april 2019
Tijd: :17:30 – 20:00
Organisator: University of Twente
Locatie: Design Lab University of Twente
Hengelosestraat 500
7521 AN Enschede

Just days before, the University of Twente announced this research in an April 16, 2019 news item on Naowerk (Note: A link has been removed),

A tattoo that is warning you for too many hours of sunlight exposure, or is alerting you for taking your medication? Next to their cosmetic role, tattoos could get new functionality using intelligent ink. That would require more precise and less invasive injection technique.

Researchers of the University of Twente now develop a micro-jet injection technology that doesn’t use needles at all. Instead, an ultrafast liquid jet with the thickness of a human hair penetrates the skin. It isn’t painful and there is less waste.

In their new publication in the American Journal of Physics (“High speed imaging of solid needle and liquid micro-jet injections”), the scientists compare both the needle and the fluid jet approach.

Here’s an image provided by the researchers which illustrates the technique they have developed,

Working principle of needle-free injection: laser heating the fluid.The growing bubble pushes out the fluid (medicine or ink) at very high speed. Courtesy: University of Twente

An April 15, 2019 University of Twente press release, which originated the news item, provides more detail about tattoos and the research leading to ‘need-free’ tattoos,

Ötzi the Iceman already had, over 5000 years ago, dozens of simple tattoos on his body, apparently for pain relief. Since the classic ‘anchor’ tattoo that sailors had on their arms, tattoos have become more and more common. About 44 million Europeans wear one or more of them. Despite its wider acceptance in society, the underlying technique didn’t change and still has health risks. One or more moving needles put ink underneath the skin surface. This is painful and can damage the skin. Apart from that, needles have to be disposed of in a responsible way, and quite some ink is wasted. The alternative that David Fernández Rivas and his colleagues are developing, doesn’t use any needles. In their new paper, they compare this new approach with classic needle technology, on an artificial skin material and using high speed images. Remarkably, according to Fernández Rivas, the classic needle technology has never been subject of research in such a thorough way, using high speed images.

Fast fluid jet

The new technique employs a laser for rapidly heating a fluid that is inside a microchannel on a glass chip. Heated above the boiling point, a vapour bubble forms and grows, pushing the liquid out at speeds up to 100 meter per second (360 km/h). The jet, about the diameter of a human hair, is capable of going through human skin. “You don’t feel much of it, no more than a mosquito bite”, say Fernandez Rivas.

The researchers did their experiments with a number of commercially available inks. Compared to a tattoo machine, the micro-jet consumes a small amount of energy. What’s more important, it minimizes skin damage and the injection efficiency is much higher, there is no loss of fluids. And there is no risk of contaminated needles. The current microjet is a single one, while tattooing is often done using multiple needles with different types or colours of ink. Also, the volume that can be ‘delivered’ by the microjet has to be increased. These are next steps in developing the needle-free technology.

Skin treatment

In today’s medical world, tattoo-resembling techniques are used for treatment of skin, masking scars, or treating hair diseases. These are other areas in which the new technique can be used, as well as in vaccination. A challenging idea is using tattoos for cosmetic purposes and as health sensors at the same time. What if ink is light-sensitive or responds to certain substances that are present in the skin or in sweat?

On this new approach, scientists, students, entrepreneurs and tattoo artists join a special event ‘The future under our skin’, organized by David Fernandez Rivas.

Research has been done in the Mesoscale Chemical Systems group, part of UT’s MESA+ Institute.

Here’s a link to an d a citation for the paper,

High speed imaging of solid needle and liquid micro-jet injections by Loreto Oyarte Gálveza, Maria Brió Pérez, and David Fernández Rivas. Journal of Applied Physics 125, 144504 (2019); Volume 125, Issue 14 DOI: 10.1063/1.5074176 https://doi.org/10.1063/1.5074176 Free Published Online: 09 April 2019

This paper appears to be open access.

Cyborgs based on melanin circuits

Pigments for biocompatible electronics? According to a March 26, 2019 news item on Nanowerk this is a distinct possibility (Note: A link has been removed),

The dark brown melanin pigment, eumelanin, colors hair and eyes, and protects our skin from sun damage. It has also long been known to conduct electricity, but too little for any useful application – until now.

In a landmark study published in Frontiers in Chemistry (“Evidence of Unprecedented High Electronic Conductivity in Mammalian Pigment Based Eumelanin Thin Films After Thermal Annealing in Vacuum”), Italian researchers subtly modified the structure of eumelanin by heating it in a vacuum.

“Our process produced a billion-fold increase in the electrical conductivity of eumelanin,” say study senior authors Dr. Alessandro Pezzella of University of Naples Federico II and Dr. Paolo Tassini of Italian National Agency for New Technologies, Energy and Sustainable Economic Development. “This makes possible the long-anticipated design of melanin-based electronics, which can be used for implanted devices due to the pigment’s biocompatibility.”

This is a rather dreamy image to illustrate the point,

Despite extensive research on the structure of melanin, nobody has yet managed to harness its potential in implantable electronics. Image: Shutterstock. [downloaded from https://blog.frontiersin.org/2019/03/26/will-cyborgs-circuits-be-made-from-melanin/]

A March 26, 2019 Frontiers in Chemistry (journal) press release (also on EurekAlert), which originated the news item, expands on the theme,

A young Pezzella had not even begun school when scientists first discovered that a type of melanin can conduct electricity. Excitement quickly rose around the discovery because eumelanin – the dark brown pigment found in hair, skin and eyes – is fully biocompatible.

“Melanins occur naturally in virtually all forms of life. They are non-toxic and do not elicit an immune reaction,” explains Pezzella. “Out in the environment, they are also completely biodegradable.”

Decades later, and despite extensive research on the structure of melanin, nobody has managed to harness its potential in implantable electronics.

“To date, conductivity of synthetic as well as natural eumelanin has been far too low for valuable applications,” he adds.

Some researchers tried to increase the conductivity of eumelanin by combining it with metals, or super-heating it into a graphene-like material – but what they were left with was not truly the biocompatible conducting material promised.

Determined to find the real deal, the Neapolitan group considered the structure of eumelanin.

“All of the chemical and physical analyses of eumelanin paint the same picture – of electron-sharing molecular sheets, stacked messily together. The answer seemed obvious: neaten the stacks and align the sheets, so they can all share electrons – then the electricity will flow.”

This process, called annealing, is used already to increase electrical conductivity and other properties in materials such as metals.

For the first time, the researchers put films of synthetic eumelanin through an annealing process under high vacuum to neaten them up – a little like hair straightening, but with only the pigment.

“We heated these eumelanin films – no thicker than a bacterium – under vacuum conditions, from 30 min up to 6 hours,” describes Tassini. “We call the resulting material High Vacuum Annealed Eumelanin, HVAE.”

The annealing worked wonders for eumelanin: the films slimmed down by more than half, and picked up quite a tan.

“The HVAE films were now dark brown and about as thick as a virus,” Tassini reports.

Crucially, the films had not simply been burnt to a crisp.

“All our various analyses agree that these changes reflect reorganization of eumelanin molecules from a random orientation to a uniform, electron-sharing stack. The annealing temperatures were too low to break up the eumelanin, and we detected no combustion to elemental carbon.”

Having achieved the intended structural changes to eumelanin, the researchers proved their hypothesis in spectacular fashion.

“The conductivity of the films increased billion-fold to an unprecedented value of over 300 S/cm, after annealing at 600°C for 2 hours,” Pezzella confirms.

Although well short of most metal conductors – copper has a conductivity of around 6 x 107 S/cm – this finding launches eumelanin well into a useful range for bioelectronics.

What’s more, the conductivity of HVAE was tunable according to the annealing conditions.

“The conductivity of the films increased with increasing temperature, from 1000-fold at 200°C. This opens the possibility of tailoring eumelanin for a wide range of applications in organic electronics and bioelectronics. It also strongly supports the conclusion from structural analysis that annealing reorganized the films, rather than burning them.”

There is one potential dampener: immersion of the films in water results in a marked decrease in conductivity.

“This contrasts with untreated eumelanin which, albeit in a much lower range, becomes more conductive with hydration (humidity) because it conducts electricity via ions as well as electrons. Further research is needed to fully understand the ionic vs. electronic contributions in eumelanin conductivity, which could be key to how eumelanin is used practically in implantable electronics.” concludes Pezzella.

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

Evidence of Unprecedented High Electronic Conductivity in Mammalian Pigment Based Eumelanin Thin Films After Thermal Annealing in Vacuum by Ludovico Migliaccio, Paola Manini, Davide Altamura, Cinzia Giannini, Paolo Tassini, Maria Grazia Maglione, Carla Minarini, and Alessandro Pezzella. Front. Chem., 26 March 2019 DOI: https://doi.org/10.3389/fchem.2019.00162

This paper is open access.