Category Archives: human enhancement

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).

World’s first liquid retina prosthesis

The new artificial liquid retina is biomimetic and consists of an aqueous component in which photoactive polymeric nanoparticles (whose size is of 350 nanometres, thus about 1/100 of the diameter of a hair) are suspended, going to replace the damaged photoreceptors. Credit: IIT-Istituto Italiano di Tecnologia [image downloaded from https://www.medgadget.com/2020/06/injectable-liquid-prosthesis-to-treat-retinal-diseases-developed.html]

A June 29, 2020 news item on Nanowerk announces the world’s first liquid retina prosthesis,

Researchers at IIT-Istituto Italiano di Tecnologia (Italian Institute of Technology) has led to the revolutionary development of an artificial liquid retinal prosthesis to counteract the effects of diseases such as retinitis pigmentosa and age-related macular degeneration that cause the progressive degeneration of photoreceptors of the retina, resulting in blindness.

The multidisciplinary team is composed by researchers from the IIT’s Center for Synaptic Neuroscience and Technology in Genoa coordinated by Fabio Benfenati and a team from the IIT’s Center for Nano Science and Technology in Milan coordinated by Guglielmo Lanzani, and it also involves the IRCCS Ospedale Sacrocuore Don Calabria in Negrar (Verona) with the team lead by Grazia Pertile, the IRCCS Ospedale Policlinico San Martino in Genoa and the CNR in Bologna. The research has been supported by Fondazione 13 Marzo Onlus, Fondazione Ra.Mo., Rare Partners srl and Fondazione Cariplo.

The study represents the state of the art in retinal prosthetics and is an evolution of the planar artificial retinal model developed by the same team in 2017 and based on organic semiconductor materials (Nature Materials 2017, 16: 681-689).

A June 30, 2020 IIT-Istituto Italiano di Tecnologia (Italian Institute of Technology) press release (also on EurekAlert but published June 29, 2020) provides more detail,

The “second generation” artificial retina is biomimetic, offers high spatial resolution and consists of an aqueous component in which photoactive polymeric nanoparticles (whose size is of 350 nanometres, thus about 1/100 of the diameter of a hair) are suspended, going to replace the damaged photoreceptors.

The experimental results show that the natural light stimulation of nanoparticles, in fact, causes the activation of retinal neurons spared from degeneration, thus mimicking the functioning of photoreceptors in healthy subjects.

Compared to other existing approaches, the new liquid nature of the prosthesis ensures fast and less traumatic surgery that consist of microinjections of nanoparticles directly under the retina, where they remain trapped and replace the degenerated photoreceptors; this method also ensures an increased effectiveness.

The data collected show also that the innovative experimental technique represents a valid alternative to the methods used to date to restore the photoreceptive capacity of retinal neurons while preserving their spatial resolution, laying a solid foundation for future clinical trials in humans. Moreover, the development of these photosensitive nanomaterials opens the way to new future applications in neuroscience and medicine.

“Our experimental results highlight the potential relevance of nanomaterials in the development of second-generation retinal prostheses to treat degenerative retinal blindness, and represents a major step forward” Fabio Benfenati commented. “The creation of a liquid artificial retinal implant has great potential to ensure a wide-field vision and high-resolution vision. Enclosing the photoactive polymers in particles that are smaller than the photoreceptors, increases the active surface of interaction with the retinal neurons, allows to easily cover the entire retinal surface and to scale the photoactivation at the level of a single photoreceptor.”

“In this research we have applied nanotechnology to medicine” concludes Guglielmo Lanzani. “In particular in our labs we have realized polymer nanoparticles that behave like tiny photovoltaic cells, based on carbon and hydrogen, fundamental components of the biochemistry of life. Once injected into the retina, these nanoparticles form small aggregates the size of which is comparable to that of neurons, that effectively behave like photoreceptors.”

“The surgical procedure for the subretinal injection of photoactive nanoparticles is minimally invasive and potentially replicable over time, unlike planar retinal prostheses” adds Grazia Pertile, Director at Operating Unit of Ophthalmology at IRCCS Ospedale Sacro Cuore Don Calabria. “At the same time maintaining the advantages of polymeric prosthesis, which is naturally sensitive to the light entering the eye and does not require glasses, cameras or external energy sources.”

The research study is based on preclinical models and further experimentations will be fundamental to make the technique a clinical treatment for diseases such as retinitis pigmentosa and age-related macular degeneration.

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

Subretinally injected semiconducting polymer nanoparticles rescue vision in a rat model of retinal dystrophy by José Fernando Maya-Vetencourt, Giovanni Manfredi, Maurizio Mete, Elisabetta Colombo, Mattia Bramini, Stefano Di Marco, Dmytro Shmal, Giulia Mantero, Michele Dipalo, Anna Rocchi, Mattia L. DiFrancesco, Ermanno D. Papaleo, Angela Russo, Jonathan Barsotti, Cyril Eleftheriou, Francesca Di Maria, Vanessa Cossu, Fabio Piazza, Laura Emionite, Flavia Ticconi, Cecilia Marini, Gianmario Sambuceti, Grazia Pertile, Guglielmo Lanzani & Fabio Benfenati. Nature Nanotechnology (2020) DOI: https://doi.org/10.1038/s41565-020-0696-3 Published: 29 June 2020

This paper is behind a paywall.

Living with a mind-controlled prosthetic

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

More about: How the technology works:

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

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

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

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

More about: How the artificial sensation is experienced:

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

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

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

This paper is behind a paywall.

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.