Category Archives: medicine

Neural (brain) implants and hype (long read)

There was a big splash a few weeks ago when it was announced that Neuralink’s (Elon Musk company) brain implant had been surgically inserted into its first human patient.

Getting approval

David Tuffley, senior lecturer in Applied Ethics & CyberSecurity at Griffith University (Australia), provides a good overview of the road Neuralink took to getting FDA (US Food and Drug Administration) approval for human clinical trials in his May 29, 2023 essay for The Conversation, Note: Links have been removed,

Since its founding in 2016, Elon Musk’s neurotechnology company Neuralink has had the ambitious mission to build a next-generation brain implant with at least 100 times more brain connections than devices currently approved by the US Food and Drug Administration (FDA).

The company has now reached a significant milestone, having received FDA approval to begin human trials. So what were the issues keeping the technology in the pre-clinical trial phase for as long as it was? And have these concerns been addressed?

Neuralink is making a Class III medical device known as a brain-computer interface (BCI). The device connects the brain to an external computer via a Bluetooth signal, enabling continuous communication back and forth.

The device itself is a coin-sized unit called a Link. It’s implanted within a small disk-shaped cutout in the skull using a precision surgical robot. The robot splices a thousand tiny threads from the Link to certain neurons in the brain. [emphasis mine] Each thread is about a quarter the diameter of a human hair.

The company says the device could enable precise control of prosthetic limbs, giving amputees natural motor skills. It could revolutionise treatment for conditions such as Parkinson’s disease, epilepsy and spinal cord injuries. It also shows some promise for potential treatment of obesity, autism, depression, schizophrenia and tinnitus.

Several other neurotechnology companies and researchers have already developed BCI technologies that have helped people with limited mobility regain movement and complete daily tasks.

In February 2021, Musk said Neuralink was working with the FDA to secure permission to start initial human trials later that year. But human trials didn’t commence in 2021.

Then, in March 2022, Neuralink made a further application to the FDA to establish its readiness to begin humans trials.

One year and three months later, on May 25 2023, Neuralink finally received FDA approval for its first human clinical trial. Given how hard Neuralink has pushed for permission to begin, we can assume it will begin very soon. [emphasis mine]

The approval has come less than six months after the US Office of the Inspector General launched an investigation into Neuralink over potential animal welfare violations. [emphasis mine]

In accessible language, Tuffley goes on to discuss the FDA’s specific technical issues with implants and how they were addressed in his May 29, 2023 essay.

More about how Neuralink’s implant works and some concerns

Canadian Broadcasting Corporation (CBC) journalist Andrew Chang offers an almost 13 minute video, “Neuralink brain chip’s first human patient. How does it work?” Chang is a little overenthused for my taste but he offers some good information about neural implants, along with informative graphics in his presentation.

So, Tuffley was right about Neuralink getting ready quickly for human clinical trials as you can guess from the title of Chang’s CBC video.

Jennifer Korn announced that recruitment had started in her September 20, 2023 article for CNN (Cable News Network), Note: Links have been removed,

Elon Musk’s controversial biotechnology startup Neuralink opened up recruitment for its first human clinical trial Tuesday, according to a company blog.

After receiving approval from an independent review board, Neuralink is set to begin offering brain implants to paralysis patients as part of the PRIME Study, the company said. PRIME, short for Precise Robotically Implanted Brain-Computer Interface, is being carried out to evaluate both the safety and functionality of the implant.

Trial patients will have a chip surgically placed in the part of the brain that controls the intention to move. The chip, installed by a robot, will then record and send brain signals to an app, with the initial goal being “to grant people the ability to control a computer cursor or keyboard using their thoughts alone,” the company wrote.

Those with quadriplegia [sometimes known as tetraplegia] due to cervical spinal cord injury or amyotrophic lateral sclerosis (ALS) may qualify for the six-year-long study – 18 months of at-home and clinic visits followed by follow-up visits over five years. Interested people can sign up in the patient registry on Neuralink’s website.

Musk has been working on Neuralink’s goal of using implants to connect the human brain to a computer for five years, but the company so far has only tested on animals. The company also faced scrutiny after a monkey died in project testing in 2022 as part of efforts to get the animal to play Pong, one of the first video games.

I mentioned three Reuters investigative journalists who were reporting on Neuralink’s animal abuse allegations (emphasized in Tuffley’s essay) in a July 7, 2023 posting, “Global dialogue on the ethics of neurotechnology on July 13, 2023 led by UNESCO.” Later that year, Neuralink was cleared by the US Department of Agriculture (see September 24,, 2023 article by Mahnoor Jehangir for BNN Breaking).

Plus, Neuralink was being investigated over more allegations according to a February 9, 2023 article by Rachel Levy for Reuters, this time regarding hazardous pathogens,

The U.S. Department of Transportation said on Thursday it is investigating Elon Musk’s brain-implant company Neuralink over the potentially illegal movement of hazardous pathogens.

A Department of Transportation spokesperson told Reuters about the probe after the Physicians Committee of Responsible Medicine (PCRM), an animal-welfare advocacy group,wrote to Secretary of Transportation Pete Buttigieg, opens new tab earlier on Thursday to alert it of records it obtained on the matter.

PCRM said it obtained emails and other documents that suggest unsafe packaging and movement of implants removed from the brains of monkeys. These implants may have carried infectious diseases in violation of federal law, PCRM said.

There’s an update about the hazardous materials in the next section. Spoiler alert, the company got fined.

Neuralink’s first human implant

A January 30, 2024 article (Associated Press with files from Reuters) on the Canadian Broadcasting Corporation’s (CBC) online news webspace heralded the latest about Neurlink’s human clinical trials,

The first human patient received an implant from Elon Musk’s computer-brain interface company Neuralink over the weekend, the billionaire says.

In a post Monday [January 29, 2024] on X, the platform formerly known as Twitter, Musk said that the patient received the implant the day prior and was “recovering well.” He added that “initial results show promising neuron spike detection.”

Spikes are activity by neurons, which the National Institutes of Health describe as cells that use electrical and chemical signals to send information around the brain and to the body.

The billionaire, who owns X and co-founded Neuralink, did not provide additional details about the patient.

When Neuralink announced in September [2023] that it would begin recruiting people, the company said it was searching for individuals with quadriplegia due to cervical spinal cord injury or amyotrophic lateral sclerosis, commonly known as ALS or Lou Gehrig’s disease.

Neuralink reposted Musk’s Monday [January 29, 2024] post on X, but did not publish any additional statements acknowledging the human implant. The company did not immediately respond to requests for comment from The Associated Press or Reuters on Tuesday [January 30, 2024].

In a separate Monday [January 29, 2024] post on X, Musk said that the first Neuralink product is called “Telepathy” — which, he said, will enable users to control their phones or computers “just by thinking.” He said initial users would be those who have lost use of their limbs.

The startup’s PRIME Study is a trial for its wireless brain-computer interface to evaluate the safety of the implant and surgical robot.

Now for the hazardous materials, January 30, 2024 article, Note: A link has been removed,

Earlier this month [January 2024], a Reuters investigation found that Neuralink was fined for violating U.S. Department of Transportation (DOT) rules regarding the movement of hazardous materials. During inspections of the company’s facilities in Texas and California in February 2023, DOT investigators found the company had failed to register itself as a transporter of hazardous material.

They also found improper packaging of hazardous waste, including the flammable liquid Xylene. Xylene can cause headaches, dizziness, confusion, loss of muscle co-ordination and even death, according to the U.S. Centers for Disease Control and Prevention.

The records do not say why Neuralink would need to transport hazardous materials or whether any harm resulted from the violations.

Skeptical thoughts about Elon Musk and Neuralink

Earlier this month (February 2024), the British Broadcasting Corporation (BBC) published an article by health reporters, Jim Reed and Joe McFadden, that highlights the history of brain implants, the possibilities, and notes some of Elon Musk’s more outrageous claims for Neuralink’s brain implants,

Elon Musk is no stranger to bold claims – from his plans to colonise Mars to his dreams of building transport links underneath our biggest cities. This week the world’s richest man said his Neuralink division had successfully implanted its first wireless brain chip into a human.

Is he right when he says this technology could – in the long term – save the human race itself?

Sticking electrodes into brain tissue is really nothing new.

In the 1960s and 70s electrical stimulation was used to trigger or suppress aggressive behaviour in cats. By the early 2000s monkeys were being trained to move a cursor around a computer screen using just their thoughts.

“It’s nothing novel, but implantable technology takes a long time to mature, and reach a stage where companies have all the pieces of the puzzle, and can really start to put them together,” says Anne Vanhoestenberghe, professor of active implantable medical devices, at King’s College London.

Neuralink is one of a growing number of companies and university departments attempting to refine and ultimately commercialise this technology. The focus, at least to start with, is on paralysis and the treatment of complex neurological conditions.

Reed and McFadden’s February 2024 BBC article describes a few of the other brain implant efforts, Note: Links have been removed,

One of its [Neuralink’s] main rivals, a start-up called Synchron backed by funding from investment firms controlled by Bill Gates and Jeff Bezos, has already implanted its stent-like device into 10 patients.

Back in December 2021, Philip O’Keefe, a 62-year old Australian who lives with a form of motor neurone disease, composed the first tweet using just his thoughts to control a cursor.

And researchers at Lausanne University in Switzerland have shown it is possible for a paralysed man to walk again by implanting multiple devices to bypass damage caused by a cycling accident.

In a research paper published this year, they demonstrated a signal could be beamed down from a device in his brain to a second device implanted at the base of his spine, which could then trigger his limbs to move.

Some people living with spinal injuries are sceptical about the sudden interest in this new kind of technology.

“These breakthroughs get announced time and time again and don’t seem to be getting any further along,” says Glyn Hayes, who was paralysed in a motorbike accident in 2017, and now runs public affairs for the Spinal Injuries Association.

If I could have anything back, it wouldn’t be the ability to walk. It would be putting more money into a way of removing nerve pain, for example, or ways to improve bowel, bladder and sexual function.” [emphasis mine]

Musk, however, is focused on something far more grand for Neuralink implants, from Reed and McFadden’s February 2024 BBC article, Note: A link has been removed,

But for Elon Musk, “solving” brain and spinal injuries is just the first step for Neuralink.

The longer-term goal is “human/AI symbiosis” [emphasis mine], something he describes as “species-level important”.

Musk himself has already talked about a future where his device could allow people to communicate with a phone or computer “faster than a speed typist or auctioneer”.

In the past, he has even said saving and replaying memories may be possible, although he recognised “this is sounding increasingly like a Black Mirror episode.”

One of the experts quoted in Reed and McFadden’s February 2024 BBC article asks a pointed question,

… “At the moment, I’m struggling to see an application that a consumer would benefit from, where they would take the risk of invasive surgery,” says Prof Vanhoestenberghe.

“You’ve got to ask yourself, would you risk brain surgery just to be able to order a pizza on your phone?”

Rae Hodge’s February 11, 2024 article about Elon Musk and his hyped up Neuralink implant for Salon is worth reading in its entirety but for those who don’t have the time or need a little persuading, here are a few excerpts, Note 1: This is a warning; Hodge provides more detail about the animal cruelty allegations; Note 2: Links have been removed,

Elon Musk’s controversial brain-computer interface (BCI) tech, Neuralink, has supposedly been implanted in its first recipient — and as much as I want to see progress for treatment of paralysis and neurodegenerative disease, I’m not celebrating. I bet the neuroscientists he reportedly drove out of the company aren’t either, especially not after seeing the gruesome torture of test monkeys and apparent cover-up that paved the way for this moment. 

All of which is an ethics horror show on its own. But the timing of Musk’s overhyped implant announcement gives it an additional insulting subtext. Football players are currently in a battle for their lives against concussion-based brain diseases that plague autopsy reports of former NFL players. And Musk’s boast of false hope came just two weeks before living players take the field in the biggest and most brutal game of the year. [2024 Super Bowl LVIII]

ESPN’s Kevin Seifert reports neuro-damage is up this year as “players suffered a total of 52 concussions from the start of training camp to the beginning of the regular season. The combined total of 213 preseason and regular season concussions was 14% higher than 2021 but within range of the three-year average from 2018 to 2020 (203).”

I’m a big fan of body-tech: pacemakers, 3D-printed hips and prosthetic limbs that allow you to wear your wedding ring again after 17 years. Same for brain chips. But BCI is the slow-moving front of body-tech development for good reason. The brain is too understudied. Consequences of the wrong move are dire. Overpromising marketable results on profit-driven timelines — on the backs of such a small community of researchers in a relatively new field — would be either idiotic or fiendish. 

Brown University’s research in the sector goes back to the 1990s. Since the emergence of a floodgate-opening 2002 study and the first implant in 2004 by med-tech company BrainGate, more promising results have inspired broader investment into careful research. But BrainGate’s clinical trials started back in 2009, and as noted by Business Insider’s Hilary Brueck, are expected to continue until 2038 — with only 15 participants who have devices installed. 

Anne Vanhoestenberghe is a professor of active implantable medical devices at King’s College London. In a recent release, she cautioned against the kind of hype peddled by Musk.

“Whilst there are a few other companies already using their devices in humans and the neuroscience community have made remarkable achievements with those devices, the potential benefits are still significantly limited by technology,” she said. “Developing and validating core technology for long term use in humans takes time and we need more investments to ensure we do the work that will underpin the next generation of BCIs.” 

Neuralink is a metal coin in your head that connects to something as flimsy as an app. And we’ve seen how Elon treats those. We’ve also seen corporate goons steal a veteran’s prosthetic legs — and companies turn brain surgeons and dentists into repo-men by having them yank anti-epilepsy chips out of people’s skulls, and dentures out of their mouths. 

“I think we have a chance with Neuralink to restore full-body functionality to someone who has a spinal cord injury,” Musk said at a 2023 tech summit, adding that the chip could possibly “make up for whatever lost capacity somebody has.”

Maybe BCI can. But only in the careful hands of scientists who don’t have Musk squawking “go faster!” over their shoulders. His greedy frustration with the speed of BCI science is telling, as is the animal cruelty it reportedly prompted.

There have been other examples of Musk’s grandiosity. Notably, David Lee expressed skepticism about hyperloop in his August 13, 2013 article for BBC news online

Is Elon Musk’s Hyperloop just a pipe dream?

Much like the pun in the headline, the bright idea of transporting people using some kind of vacuum-like tube is neither new nor imaginative.

There was Robert Goddard, considered the “father of modern rocket propulsion”, who claimed in 1909 that his vacuum system could suck passengers from Boston to New York at 1,200mph.

And then there were Soviet plans for an amphibious monorail  – mooted in 1934  – in which two long pods would start their journey attached to a metal track before flying off the end and slipping into the water like a two-fingered Kit Kat dropped into some tea.

So ever since inventor and entrepreneur Elon Musk hit the world’s media with his plans for the Hyperloop, a healthy dose of scepticism has been in the air.

“This is by no means a new idea,” says Rod Muttram, formerly of Bombardier Transportation and Railtrack.

“It has been previously suggested as a possible transatlantic transport system. The only novel feature I see is the proposal to put the tubes above existing roads.”

Here’s the latest I’ve found on hyperloop, from the Hyperloop Wikipedia entry,

As of 2024, some companies continued to pursue technology development under the hyperloop moniker, however, one of the biggest, well funded players, Hyperloop One, declared bankruptcy and ceased operations in 2023.[15]

Musk is impatient and impulsive as noted in a September 12, 2023 posting by Mike Masnick on Techdirt, Note: A link has been removed,

The Batshit Crazy Story Of The Day Elon Musk Decided To Personally Rip Servers Out Of A Sacramento Data Center

Back on Christmas Eve [December 24, 2022] of last year there were some reports that Elon Musk was in the process of shutting down Twitter’s Sacramento data center. In that article, a number of ex-Twitter employees were quoted about how much work it would be to do that cleanly, noting that there’s a ton of stuff hardcoded in Twitter code referring to that data center (hold that thought).

That same day, Elon tweeted out that he had “disconnected one of the more sensitive server racks.”

Masnick follows with a story of reckless behaviour from someone who should have known better.

Ethics of implants—where to look for more information

While Musk doesn’t use the term when he describes a “human/AI symbiosis” (presumably by way of a neural implant), he’s talking about a cyborg. Here’s a 2018 paper, which looks at some of the implications,

Do you want to be a cyborg? The moderating effect of ethics on neural implant acceptance by Eva Reinares-Lara, Cristina Olarte-Pascual, and Jorge Pelegrín-Borondo. Computers in Human Behavior Volume 85, August 2018, Pages 43-53 DOI: https://doi.org/10.1016/j.chb.2018.03.032

This paper is open access.

Getting back to Neuralink, I have two blog posts that discuss the company and the ethics of brain implants from way back in 2021.

First, there’s Jazzy Benes’ March 1, 2021 posting on the Santa Clara University’s Markkula Center for Applied Ethics blog. It stands out as it includes a discussion of the disabled community’s issues, Note: Links have been removed,

In the heart of Silicon Valley we are constantly enticed by the newest technological advances. With the big influencers Grimes [a Canadian musician and the mother of three children with Elon Musk] and Lil Uzi Vert publicly announcing their willingness to become experimental subjects for Elon Musk’s Neuralink brain implantation device, we are left wondering if future technology will actually give us “the knowledge of the Gods.” Is it part of the natural order for humans to become omniscient beings? Who will have access to the devices? What other ethical considerations must be discussed before releasing such technology to the public?

A significant issue that arises from developing technologies for the disabled community is the assumption that disabled persons desire the abilities of what some abled individuals may define as “normal.” Individuals with disabilities may object to technologies intended to make them fit an able-bodied norm. “Normal” is relative to each individual, and it could be potentially harmful to use a deficit view of disability, which means judging a disability as a deficiency. However, this is not to say that all disabled individuals will reject a technology that may enhance their abilities. Instead, I believe it is a consideration that must be recognized when developing technologies for the disabled community, and it can only be addressed through communication with disabled persons. As a result, I believe this is a conversation that must be had with the community for whom the technology is developed–disabled persons.

With technologies that aim to address disabilities, we walk a fine line between therapeutics and enhancement. Though not the first neural implant medical device, the Link may have been the first BCI system openly discussed for its potential transhumanism uses, such as “enhanced cognitive abilities, memory storage and retrieval, gaming, telepathy, and even symbiosis with machines.” …

Benes also discusses transhumanism, privacy issues, and consent issues. It’s a thoughtful reading experience.

Second is a July 9, 2021 posting by anonymous on the University of California at Berkeley School of Information blog which provides more insight into privacy and other issues associated with data collection (and introduced me to the concept of decisional interference),

As the development of microchips furthers and advances in neuroscience occur, the possibility for seamless brain-machine interfaces, where a device decodes inputs from the user’s brain to perform functions, becomes more of a reality. These various forms of these technologies already exist. However, technological advances have made implantable and portable devices possible. Imagine a future where humans don’t need to talk to each other, but rather can transmit their thoughts directly to another person. This idea is the eventual goal of Elon Musk, the founder of Neuralink. Currently, Neuralink is one of the main companies involved in the advancement of this type of technology. Analysis of the Neuralink’s technology and their overall mission statement provide an interesting insight into the future of this type of human-computer interface and the potential privacy and ethical concerns with this technology.

As this technology further develops, several privacy and ethical concerns come into question. To begin, using Solove’s Taxonomy as a privacy framework, many areas of potential harm are revealed. In the realm of information collection, there is much risk. Brain-computer interfaces, depending on where they are implanted, could have access to people’s most private thoughts and emotions. This information would need to be transmitted to another device for processing. The collection of this information by companies such as advertisers would represent a major breach of privacy. Additionally, there is risk to the user from information processing. These devices must work concurrently with other devices and often wirelessly. Given the widespread importance of cloud computing in much of today’s technology, offloading information from these devices to the cloud would be likely. Having the data stored in a database puts the user at the risk of secondary use if proper privacy policies are not implemented. The trove of information stored within the information collected from the brain is vast. These datasets could be combined with existing databases such as browsing history on Google to provide third parties with unimaginable context on individuals. Lastly, there is risk for information dissemination, more specifically, exposure. The information collected and processed by these devices would need to be stored digitally. Keeping such private information, even if anonymized, would be a huge potential for harm, as the contents of the information may in itself be re-identifiable to a specific individual. Lastly there is risk for invasions such as decisional interference. Brain-machine interfaces would not only be able to read information in the brain but also write information. This would allow the device to make potential emotional changes in its users, which be a major example of decisional interference. …

For the most recent Neuralink and brain implant ethics piece, there’s this February 14, 2024 essay on The Conversation, which, unusually, for this publication was solicited by the editors, Note: Links have been removed,

In January 2024, Musk announced that Neuralink implanted its first chip in a human subject’s brain. The Conversation reached out to two scholars at the University of Washington School of Medicine – Nancy Jecker, a bioethicst, and Andrew Ko, a neurosurgeon who implants brain chip devices – for their thoughts on the ethics of this new horizon in neuroscience.

Information about the implant, however, is scarce, aside from a brochure aimed at recruiting trial subjects. Neuralink did not register at ClinicalTrials.gov, as is customary, and required by some academic journals. [all emphases mine]

Some scientists are troubled by this lack of transparency. Sharing information about clinical trials is important because it helps other investigators learn about areas related to their research and can improve patient care. Academic journals can also be biased toward positive results, preventing researchers from learning from unsuccessful experiments.

Fellows at the Hastings Center, a bioethics think tank, have warned that Musk’s brand of “science by press release, while increasingly common, is not science. [emphases mine]” They advise against relying on someone with a huge financial stake in a research outcome to function as the sole source of information.

When scientific research is funded by government agencies or philanthropic groups, its aim is to promote the public good. Neuralink, on the other hand, embodies a private equity model [emphasis mine], which is becoming more common in science. Firms pooling funds from private investors to back science breakthroughs may strive to do good, but they also strive to maximize profits, which can conflict with patients’ best interests.

In 2022, the U.S. Department of Agriculture investigated animal cruelty at Neuralink, according to a Reuters report, after employees accused the company of rushing tests and botching procedures on test animals in a race for results. The agency’s inspection found no breaches, according to a letter from the USDA secretary to lawmakers, which Reuters reviewed. However, the secretary did note an “adverse surgical event” in 2019 that Neuralink had self-reported.

In a separate incident also reported by Reuters, the Department of Transportation fined Neuralink for violating rules about transporting hazardous materials, including a flammable liquid.

…the possibility that the device could be increasingly shown to be helpful for people with disabilities, but become unavailable due to loss of research funding. For patients whose access to a device is tied to a research study, the prospect of losing access after the study ends can be devastating. [emphasis mine] This raises thorny questions about whether it is ever ethical to provide early access to breakthrough medical interventions prior to their receiving full FDA approval.

Not registering a clinical trial would seem to suggest there won’t be much oversight. As for Musk’s “science by press release” activities, I hope those will be treated with more skepticism by mainstream media although that seems unlikely given the current situation with journalism (more about that in a future post).

As for the issues associated with private equity models for science research and the problem of losing access to devices after a clinical trial is ended, my April 5, 2022 posting, “Going blind when your neural implant company flirts with bankruptcy (long read)” offers some cautionary tales, in addition to being the most comprehensive piece I’ve published on ethics and brain implants.

My July 17, 2023 posting, “Unveiling the Neurotechnology Landscape: Scientific Advancements, Innovations and Major Trends—a UNESCO report” offers a brief overview of the international scene.

Communicating thoughts by means of brain implants?

The Australian military announced mind-controlled robots in Spring 2023 (see my June 13, 2023 posting) and, recently, scientists at Duke University (North Carolina, US) have announced research that may allow people who are unable to speak to communicate their thoughts, from a November 6, 2023 news item on ScienceDaily,

A speech prosthetic developed by a collaborative team of Duke neuroscientists, neurosurgeons, and engineers can translate a person’s brain signals into what they’re trying to say.

Appearing Nov. 6 [2023] in the journal Nature Communications, the new technology might one day help people unable to talk due to neurological disorders regain the ability to communicate through a brain-computer interface.

One more plastic brain for this blog,

Caption: A device no bigger than a postage stamp (dotted portion within white band) packs 128 microscopic sensors that can translate brain cell activity into what someone intends to say. Credit: Dan Vahaba/Duke University

A November 6, 2023 Duke University news release (also on EurekAlert), which originated the news item, provides more detail, Note: Links have been removed,

“There are many patients who suffer from debilitating motor disorders, like ALS (amyotrophic lateral sclerosis) or locked-in syndrome, that can impair their ability to speak,” said Gregory Cogan, Ph.D., a professor of neurology at Duke University’s School of Medicine and one of the lead researchers involved in the project. “But the current tools available to allow them to communicate are generally very slow and cumbersome.”

Imagine listening to an audiobook at half-speed. That’s the best speech decoding rate currently available, which clocks in at about 78 words per minute. People, however, speak around 150 words per minute.

The lag between spoken and decoded speech rates is partially due the relatively few brain activity sensors that can be fused onto a paper-thin piece of material that lays atop the surface of the brain. Fewer sensors provide less decipherable information to decode.

To improve on past limitations, Cogan teamed up with fellow Duke Institute for Brain Sciences faculty member Jonathan Viventi, Ph.D., whose biomedical engineering lab specializes in making high-density, ultra-thin, and flexible brain sensors.

For this project, Viventi and his team packed an impressive 256 microscopic brain sensors onto a postage stamp-sized piece of flexible, medical-grade plastic. Neurons just a grain of sand apart can have wildly different activity patterns when coordinating speech, so it’s necessary to distinguish signals from neighboring brain cells to help make accurate predictions about intended speech.

After fabricating the new implant, Cogan and Viventi teamed up with several Duke University Hospital neurosurgeons, including Derek Southwell, M.D., Ph.D., Nandan Lad, M.D., Ph.D., and Allan Friedman, M.D., who helped recruit four patients to test the implants. The experiment required the researchers to place the device temporarily in patients who were undergoing brain surgery for some other condition, such as  treating Parkinson’s disease or having a tumor removed. Time was limited for Cogan and his team to test drive their device in the OR.

“I like to compare it to a NASCAR pit crew,” Cogan said. “We don’t want to add any extra time to the operating procedure, so we had to be in and out within 15 minutes. As soon as the surgeon and the medical team said ‘Go!’ we rushed into action and the patient performed the task.”

The task was a simple listen-and-repeat activity. Participants heard a series of nonsense words, like “ava,” “kug,” or “vip,” and then spoke each one aloud. The device recorded activity from each patient’s speech motor cortex as it coordinated nearly 100 muscles that move the lips, tongue, jaw, and larynx.

Afterwards, Suseendrakumar Duraivel, the first author of the new report and a biomedical engineering graduate student at Duke, took the neural and speech data from the surgery suite and fed it into a machine learning algorithm to see how accurately it could predict what sound was being made, based only on the brain activity recordings.

For some sounds and participants, like /g/ in the word “gak,”  the decoder got it right 84% of the time when it was the first sound in a string of three that made up a given nonsense word.

Accuracy dropped, though, as the decoder parsed out sounds in the middle or at the end of a nonsense word. It also struggled if two sounds were similar, like /p/ and /b/.

Overall, the decoder was accurate 40% of the time. That may seem like a humble test score, but it was quite impressive given that similar brain-to-speech technical feats require hours or days-worth of data to draw from. The speech decoding algorithm Duraivel used, however, was working with only 90 seconds of spoken data from the 15-minute test.

Duraivel and his mentors are excited about making a cordless version of the device with a recent $2.4M grant from the National Institutes of Health.

“We’re now developing the same kind of recording devices, but without any wires,” Cogan said. “You’d be able to move around, and you wouldn’t have to be tied to an electrical outlet, which is really exciting.”

While their work is encouraging, there’s still a long way to go for Viventi and Cogan’s speech prosthetic to hit the shelves anytime soon.

“We’re at the point where it’s still much slower than natural speech,” Viventi said in a recent Duke Magazine piece about the technology, “but you can see the trajectory where you might be able to get there.”

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

High-resolution neural recordings improve the accuracy of speech decoding by Suseendrakumar Duraivel, Shervin Rahimpour, Chia-Han Chiang, Michael Trumpis, Charles Wang, Katrina Barth, Stephen C. Harward, Shivanand P. Lad, Allan H. Friedman, Derek G. Southwell, Saurabh R. Sinha, Jonathan Viventi & Gregory B. Cogan. Nature Communications volume 14, Article number: 6938 (2023) DO: Ihttps://doi.org/10.1038/s41467-023-42555-1 Published: 06 November 2023

This paper is open access.

Health/science journalists/editors: deadline is March 22, 2024 for media boot camp in Boston, Massachusetts

A February 14, 2023 Broad Institute news release presents an exciting opportunity for health/science journalists and editors,

The Broad Institute of MIT [Massachusetts Institute of Technology] and Harvard is now accepting applications for its 2024 Media Boot Camp.

This annual program connects health/science journalists and editors with faculty from the Broad Institute, Massachusetts Institute of Technology, Harvard University, and Harvard’s teaching hospitals for a two-day event exploring the latest advances in genomics and biomedicine. Journalists will explore possible future storylines, gain fundamental background knowledge, and build relationships with researchers. The program format includes presentations, discussions, and lab tours.

The 2024 Media Boot Camp will take place in person at the Broad Institute in Cambridge, MA on Thursday, May 16 and Friday, May 17 (with an evening welcome reception on Wednesday, May 15).

APPLICATION DEADLINE IS FRIDAY, MARCH 22 (5:00 PM US EASTERN TIME).

2024 Boot Camp topics include:

  • Gene editing
  • New approaches for therapeutic delivery  
  • Cancer biology, drug development
  • Data sciences, machine learning
  • Neurobiology (stem cell models of psychiatric disorders)
  • Antibiotic resistance, microbial biology
  • Medical and population genetics, genomic medicine

Current speakers include: Mimi Bandopadhayay, Clare Bernard,Roby Bhattacharyya, Todd Golub, Laura Kiessling, Eric Lander,David Liu, Ralda Nehme,Heidi Rehm, William Sellers, Feng Zhang, with potentially more to come.

This Media Boot Camp is an educational offering. All presentations are on-background.

Hotel accommodations and meals during the program will be provided by the Broad Institute. Attendees must cover travel costs to and from Boston.

Application Process

By Friday, March 22 [2024] (5:00 PM US Eastern time [2 pm PT]), please send at least one paragraph describing your interest in the program and how you hope it will benefit your reporting, as well as three recent news clips, to David Cameron, Director of External Communications, dcameron@broadinstitute.org

Please contact David at dcameron@broadinstitute.org, or 617-714-7184 with any questions.

I couldn’t find details about eligibility, that said, I wish you good luck with your ‘paragraph and three recent clips’ submission.

Mending a broken heart with hydrogels and cellulose nanocrystals (CNC)

Courtesy: University of Waterloo

This February 12, 2024 news item on ScienceDaily highlights work from the University of Waterloo,

You can mend a broken heart this valentine’s day now that researchers invented a new hydrogel that can be used to heal damaged heart tissue and improve cancer treatments.

University of Waterloo chemical engineering researcher Dr. Elisabeth Prince teamed up with researchers from the University of Toronto and Duke University to design the synthetic material made using cellulose nanocrystals [CNC], which are derived from wood pulp.

A February 12, 2024 University of Waterloo news release (also on EurekAlert), which originated the news item, fills in some details,

The material is engineered to replicate the fibrous nanostructures and properties of human tissues, thereby recreating its unique biomechanical properties.

“Cancer is a diverse disease and two patients with the same type of cancer will often respond to the same treatment in very different ways,” Prince said. “Tumour organoids are essentially a miniaturized version of an individual patient’s tumour that can be used for drug testing, which could allow researchers to develop personalized therapies for a specific patient.”

As director of the Prince Polymer Materials Lab, Prince designs synthetic biomimetic hydrogels for biomedical applications. The hydrogels have a nanofibrous architecture with large pores for nutrient and waste transport, which affect mechanical properties and cell interaction. 

Prince, a professor in Waterloo’s Department of Chemical Engineering, utilized these human-tissue mimetic hydrogels to promote the growth of small-scale tumour replicas derived from donated tumour tissue. 

She aims to test the effectiveness of cancer treatments on the mini-tumour organoids before administering the treatment to patients, potentially allowing for personalized cancer therapies. This research was conducted alongside Professor David Cescon at the Princess Margaret Cancer Center.

Prince’s research group at Waterloo is developing similar biomimetic hydrogels to be injectable for drug delivery and regenerative medical applications as Waterloo researchers continue to lead health innovation in Canada.

Her research aims to use injected filamentous hydrogel material to regrow heart tissue damaged after a heart attack. She used nanofibers as a scaffolding for the regrowth and healing of damaged heart tissue. 

“We are building on the work that I started during my PhD to design human-tissue mimetic hydrogels that can be injected into the human body to deliver therapeutics and repair the damage caused to the heart when a patient suffers a heart attack,” Prince said.

Prince’s research is unique as most gels currently used in tissue engineering or 3D cell culture don’t possess this nanofibrous architecture. Prince’s group uses nanoparticles and polymers as building blocks for materials and develops chemistry for nanostructures that accurately mimic human tissues.

The next step in Prince’s research is to use conductive nanoparticles to make electrically conductive nanofibrous gels that can be used to heal heart and skeletal muscle tissue.

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

Nanocolloidal hydrogel mimics the structure and nonlinear mechanical properties of biological fibrous networks by Elisabeth Prince, Sofia Morozova, Zhengkun Chen, and Eugenia Kumacheva. Proceedings of the National Academy of Sciences (PNAS) December 13, 2023 120 (51) e2220755120 DOI: https://doi.org/10.1073/pnas.2220755120

This paper is behind a paywall.

Questioning or rewriting a ‘central’ dogma of biology?

Answering the question in the head, this December 12, 2023 news item on phys.org calls into question the principle behind how medicines based on antibodies work,

Today, medicines based on antibodies—proteins that fight infection and disease—are prescribed for everything from cancer to COVID-19 to high cholesterol. The antibody drugs are supplied by genetically-engineered cells that function as tiny protein-producing factories in the laboratory.

Meanwhile, researchers have been targeting cancer, injuries to internal organs and a host of other ailments with new strategies in which similarly engineered cells are implanted directly into patients.

These biotechnology applications rely on the principle that altering a cell’s DNA to produce more of the genetic instructions for making a given protein will cause the cell to release more of that protein.

A new UCLA [University of California at Los Angeles] study suggests that—at least in one type of stem cell—the principle doesn’t necessarily hold true.

A December 11, 2023 UCLA news release, which originated the news item, delves further into the topic but first the key points are noted, Note: Links have been removed,

Key takeaways

  • Mesenchymal stem cells, found in bone marrow, secrete therapeutic proteins that could potentially help regenerate damaged tissue.
  • A UCLA study examining these cells challenges the conventional understanding of which genetic instructions prompt the release of these therapeutic proteins.
  • The findings could help advance both regenerative medicine research and the laboratory production of biologic treatments already in use.

The researchers examined mesenchymal stem cells, which reside in bone marrow and can self-renew or develop into bone, fat or muscle cells. Mesenchymal cells secrete a protein growth factor called VEGF-A, which plays a role in regenerating blood vessels and which scientists believe may have the potential to repair damage from heart attacks, kidney injuries, arterial disease in limbs and other conditions.

When the researchers compared the amount of VEGF-A that each mesenchymal cell released with the expression of genes in the same cell that code for VEGF-A, the results were surprising: Gene expression correlated only weakly with the actual secretion of the growth factor.  

The scientists identified other genes better correlating with growth factor secretion, including one that codes for a protein found on the surface of some stem cells. Isolating stem cells with that protein on their surface, the team cultivated a population that secreted VEGF-A prolifically and kept doing so days later.

The findings, published today [December 11, 2023] in Nature Nanotechnology, suggest that a fundamental assumption in biology and biotechnology may be up for reconsideration, said co-corresponding author Dino Di Carlo, the Armond and Elena Hairapetian Professor of Engineering and Medicine at the UCLA Samueli School of Engineering.

“The central dogma has been, you have instructions in the DNA, they’re transcribed to RNA, and then the RNA is translated into protein,” said Di Carlo, who is also a member of UCLA’s California NanoSystems Institute and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. “Based on this, many scientists assumed that if you had more RNA, you’d have more protein, and then more protein released from the cell. We questioned that assumption.

“It seems we can’t assume that if a gene is expressed at higher levels, there will be higher secretion of the corresponding protein. We found a clear example where that doesn’t happen, and it opens up a lot of new questions.”

The results could help make the manufacturing of antibody-based treatments more efficient and define new cellular treatments that would be more effective. Knowing the right genetic switches to flip could enable the engineering or selection of extraordinarily productive cells for making or delivering therapies.

The UCLA study was conducted using standard lab equipment augmented with a technology invented by Di Carlo and his colleagues: nanovials, microscopic bowl-shaped hydrogel containers, each of which captures a single cell and its secretions. Leveraging a new nanovial-enabled analytic method, the scientists were able to connect the amount of VEGF-A released by each one of 10,000 mesenchymal stem cells to an atlas mapping tens of thousands of genes expressed by that same cell.

“The ability to link protein secretion to gene expression on the single-cell level holds great promise for the fields of life science research and therapeutic development,” said Kathrin Plath, a UCLA professor of biological chemistry, a member of the Broad Stem Cell Research Center and a co-corresponding author of the study. “Without it, we couldn’t have arrived at the unexpected results we found in this study. Now we have an exciting opportunity to learn new things about the mechanisms underpinning the basic processes of life and use what we learn to advance human health.”

While activation of the genetic instructions for VEGF-A displayed little correlation with release of the protein, the researchers identified a cluster of 153 genes with strong links to VEGF-A secretion. Many of them are known for their function in blood vessel development and wound healing; for others, their function is currently unknown.

One of the top matches encodes a cell-surface protein, IL13RA2, whose purpose is poorly understood. Its exterior location made it simpler for the scientists to use it as a marker and separate those cells from the others. Cells with IL13RA2 showed 30% more VEGF-A secretion than cells that lacked the marker.

In a similar experiment, the researchers kept the separated cells in culture for six days. At the end of that time, cells with the marker secreted 60% more VEGF-A compared to cells without it.

Although therapies based on mesenchymal stem cells have shown promise in laboratory studies, clinical trials with human participants have shown many of these new options to be safe but not effective. The ability to sort for high VEGF-A secreters using IL13RA2 may help turn that tide.

“Identifying a subpopulation that produces more, and markers associated with that population, means you can separate them out very easily,” Di Carlo said. “A very pure population of cells that’s going to produce high levels of your therapeutic protein should make a better therapy.”

Nanovials are available commercially from Partillion Bioscience, a company co-founded by Di Carlo that started up at the CNSI’s on-campus incubator, Magnify.

The first author of the study is Shreya Udani, who earned a doctorate from UCLA in 2023. Other co-authors, all affiliated with UCLA, are staff scientist Justin Langerman; Doyeon Koo, who earned a doctorate in 2023; graduate students Sevana Baghdasarian and Citradewi Soemardy; undergraduate Brian Cheng; Simran Kang, who earned a bachelor’s degree in 2023; and Joseph de Rutte, who earned a doctorate in 2020 and is a co-founder and CEO of Partillion.

The study was supported by the National Institutes of Health and a Stem Cell Nanomedicine Planning Award funded jointly by the CNSI and the Broad Stem Cell Research Center.

Researcher Dino Di Carlo describes his work,

Nanovials, a technology created by UCLA’s Dino Di Carlo and his colleagues, allowed researchers to capture single mesenchymal cells and their secretions. Withouth these vials, which are smaller than the width of a human hair, “we couldn’t have arrived at the unexpected results we found in this study,” said UCLA’s Kathrin Plath.

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

Associating growth factor secretions and transcriptomes of single cells in nanovials using SEC-seq by Shreya Udani, Justin Langerman, Doyeon Koo, Sevana Baghdasarian, Brian Cheng, Simran Kang, Citradewi Soemardy, Joseph de Rutte, Kathrin Plath & Dino Di Carlo. Nature Nanotechnology (2023) DOI: https://doi.org/10.1038/s41565-023-01560-7 Published: 11 December 2023

This paper is behind a paywall.

As for the two companies mentioned in the news release, you find Partillion Bioscience here and Magnify at CNSI here.

“Injectable tissue prosthesis coupled with closed-loop bioelectronic system” for damaged muscle/nerve regeneration and robot-assisted rehabilitation

A fascinating new use for hyaluronic acid (usually discussed in relation to cosmetic wrinkle-reduction) has been found according to a November 1, 2023 news item on ScienceDaily.

In a recent publication in the journal Nature, researchers from the Institute of Basic Science (IBS) in South Korea have made significant strides in biomaterial technology and rehabilitation medicine. They’ve developed a novel approach to healing muscle injury by employing “injectable tissue prosthesis” in the form of conductive hydrogels and combining it with a robot-assisted rehabilitation system.

Let’s imagine you are swimming in the ocean. A giant shark approaches and bites a huge chunk of meat out of your thigh, resulting in a complete loss of motor/sensor function in your leg.

If left untreated, such severe muscle damage would result in permanent loss of function and disability.

How on Earth will you be able to recover from this kind of injury?

Traditional rehabilitation methods for these kinds of muscle injuries have long sought an efficient closed-loop gait rehabilitation system that merges lightweight exoskeletons and wearable/implantable devices.

Such assistive prosthetic system is required to aid the patients through the process of recovering sensory and motor functions linked to nerve and muscle damage.

Unfortunately, the mechanical properties and rigid nature of existing electronic materials render them incompatible with soft tissues.

This leads to friction and potential inflammation, stalling patient rehabilitation.

To overcome these limitations, the IBS researchers turned to a material commonly used as a wrinkle-smoothing filler, called hyaluronic acid.

A November 2, 2023 Institute of Basic Science (IBS) press release (also on EurekAlert but published November 1, 2023), which originated the news item, explains how hyaluronic acid helps in tissue rehabilitation and regeneration,

Using this substance [hyaluronic acid], an injectable hydrogel was developed for “tissue prostheses”, which can temporarily fill the gap of the missing muscle/nerve tissues while it regenerates. The injectable nature of this material gives it a significant advantage over traditional bioelectronic devices, which are unsuitable for narrow, deep, or small areas, and necessitate invasive surgeries.

Thanks to its highly “tissue-like” properties, this hydrogel seamlessly interfaces with biological tissues and can be easily administered to hard-to-reach body areas without surgery. The reversible and irreversible crosslinks within the hydrogel adapt to high shear stress during injection, ensuring excellent mechanical stability. This hydrogel also incorporates gold nanoparticles, which gives it decent electrical properties. Its conductive nature allows for the effective transmission of electrophysiological signals between the two ends of injured tissues. In addition, the hydrogel is biodegrdable, meaning that the patients do not need to get surgery again.

With mechanical properties akin to natural tissues, exceptional tissue adhesion, and injectable characteristics, researchers believe this material offers a novel approach to rehabilitation.

Next, the researchers put this novel idea to the test in rodent models. To simulate volumetric muscle loss injury, a large chunk of muscle has been removed from the hind legs of these animals. By injecting the hydrogel and implanting the two kinds of stretchable tissue-interfacing devices for electrical sensing and stimulation, the researchers were able to improve the gait in the “injured” rodents. The hydrogel prosthetics were combined with robot assistance, guided by muscle electromyography signals. Together, the two helped enhance the animal’s gait without nerve stimulation. Furthermore, muscle tissue regeneration was effectively improved over the long term after the conductive hydrogel was used to fill muscle damage.

The injectable conductive hydrogel developed in this study excels in electrophysiological signal recording and stimulation performance, offering the potential to expand its applications. It presents a fresh approach to the field of bioelectronic devices and holds promise as a soft tissue prosthesis for rehabilitation support.

Emphasizing the significance of the research, Professor SHIN Mikyung notes, “We’ve created an injectable, mechanically tough, and electrically conductive soft tissue prosthesis ideal for addressing severe muscle damage requiring neuromusculoskeletal rehabilitation. The development of this injectable hydrogel, utilizing a novel cross-linking method, is a notable achievement. We believe it will be applicable not only in muscles and peripheral nerves but also in various organs like the brain and heart.”

Professor SON Donghee added, “In this study, the closed-loop gait rehabilitation system entailing tough injectable hydrogel and stretchable and self-healing sensors could significantly enhance the rehabilitation prospects for patients with neurological and musculoskeletal challenges. It could also play a vital role in precise diagnosis and treatment across various organs in the human body.”

The research team is currently pursuing further studies to develop new materials for nerve and muscle tissue regeneration that can be implanted in a minimally invasive manner. They are also exploring the potential for recovery in various tissue damages through the injection of the conductive hydrogel, eliminating the need for open surgery.

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

Injectable tissue prosthesis for instantaneous closed-loop rehabilitation by Subin Jin, Heewon Choi, Duhwan Seong, Chang-Lim You, Jong-Sun Kang, Seunghyok Rho, Won Bo Lee, Donghee Son & Mikyung Shin. Nature volume 623, pages 58–65 (2023) DOI: https://doi.org/10.1038/s41586-023-06628-x Published: 01 November 2023 Issue Date: 02 November 2023

This paper is behind a paywall.

Nanoparticle treatment for rheumatoid arthritis

An October 26, 2023 news item on phys.org announced a possible new treatment for rheumatoid arthritis (RA), Note: Links have been removed,

A team of scientists [Korea] has developed a new solution for the treatment of rheumatoid arthritis (RA). The work has been published in Nature Nanotechnology.

RA is a chronic disease that, unfortunately, has no cure. The disease triggers a mix of troublesome symptoms like inflamed joints, harmful cytokines, and immune system imbalances, which work together to create a relentless cycle of worsening symptoms. While targeting some of these factors can provide short-term relief, others remain unresolved, leading to a frustrating cycle of remission and flare-ups.

One of the major hurdles in RA treatment is the inability to restore the immune system to its healthy state. This leaves the body unable to control the continuous production of harmful substances like reactive oxygen species (ROS) and inflammatory cytokines, leading to persistent inflammation and discomfort.

In essence, the ideal treatment for RA should not only provide immediate relief from inflammation and symptoms but also address the root cause by restoring the immune system to its normal, balanced state.

New nanoparticle-based system as a solution

The new platform involves immobilizing ceria nanoparticles (Ce NPs) onto mesenchymal stem cell-derived nanovesicles (MSCNVs). Both of these components can hinder different pathogenic factors, allowing them to work both individually and cooperatively to achieve a comprehensive treatment.

Caption: Schematic illustration of comprehensive and combination RA therapy by Ce-MSCNV nanoparticles. Ce-MSCNVs scavenge the over-produced ROS in an RA knee joint, induce M1 to M2 macrophage polarization for immediate relief of inflammation and symptoms, modulate DCs into tDCs, and finally induce Tregs. Credit: Institute for Basic Science

An October 27, 2023 Institute for Basic Science (IBS) press release (also on EurekAlert but published October 26, 2023), which originated the news item, provides more details about the proposed treatment,

Ce NPs – can scavenge the overproduced ROS in RA-inflicted knee joints. They also induce polarization of M1 macrophages into M2, achieving immediate relief of inflammation and symptoms.

MSCNVs – deliver immunomodulatory cytokines, which turn dendritic cells (DC) into tolerogenic dendritic cells (tDCs). This consequently generates regulatory T cells for long-term immune tolerance.

In short, this approach aims to bridge both innate and adaptive immunity to achieve both short-term pain relief, as well as convert the tissue environment into an immune-tolerant state to prevent the recurrence of symptoms.

Researchers confirmed the efficacy of this approach using a collagen-induced arthritis mouse model. The Ce-MSCNV system was able to comprehensively treat and prevent RA by simultaneously relieving the immediate and restoring T cell immunity. Supporting data suggest that improvement in conditions can be achieved after only a single-dose treatment.

The mice treated with the Ce-MSCNV combination fared far better compared to the ones only treated using the Ce NP or MSCNV group. This clearly demonstrates the synergy between anti-inflammation and immunomodulation and underlines the importance of the combined therapy for effective RA treatment. In addition, Ce-MSCNV administration prior to booster injection markedly reduced the incidence and severity of symptoms, supporting the prophylactic potential of these nanoparticles.

First author KOO Sagang stated, “One of the hardest decisions in intractable disease therapy is determining how long the treatment should be carried on. For RA, it would not be appropriate to stop treatment just because the target marker is stabilized. A safer indicator should be that the innate and adaptive components of the collapsed immune system are normalized to protect the body.”

Koo believes that the strategy adopted by Ce-MSCNVs, where different treatment mechanisms work together, provides a unique advantage in this regard. Furthermore, she predicts that a similar approach would also be applicable to other intractable, inflammatory, and autoimmune diseases for this purpose. The components within the system may also be modified. For example, other catalysts for generating ROS or other cell-derived nanovesicles could be utilized depending on the types of diseases. Overall, this study proves the potential of a hybrid nanoparticle system for the comprehensive treatment of autoimmune disease and modulation of the immune system.

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

Ceria-vesicle nanohybrid therapeutic for modulation of innate and adaptive immunity in a collagen-induced arthritis model by Sagang Koo, Hee Su Sohn, Tae Hee Kim, Siyeon Yang, Se Youn Jang, Seongryeol Ye, Boomin Choi, Soo Hyeon Kim, Kyoung Sun Park, Hyun Mu Shin, Ok Kyu Park, Cheesue Kim, Mikyung Kang, Min Soh, Jin Yoo, Dokyoon Kim, Nohyun Lee, Byung-Soo Kim, Youngmee Jung & Taeghwan Hyeon. Nature Nanotechnology (2023) DOI: https://doi.org/10.1038/s41565-023-01523-y Published: 26 October 2023

This paper is behind a paywall.

Antimicrobial ‘safe-tea’ with silver nanoparticles and green tea

This work is not about drinking tea with silver nanoparticles in it or ingesting colloidal silver by any means, a dangerous practice as Nicole Karlis’s January 7, 2024 article for Salon highlights, Note: Links have been removed,

The HBO docuseries “Love Has Won: The Cult of Mother God” begins with a jarring image. The corpse of the cult leader, Amy Carlson, laying in a bed, wrapped in blankets and string lights. She is noticeably gaunt and her face is a very blue color. When Carlson died in 2021 at the age of 45, a coroner’s report deemed her cause of death to be “alcohol abuse, anorexia and chronic colloidal silver ingestion.”

Most medical experts advise against ingesting silver — especially in large amounts. That’s because too much of it can build up in a person’s body and lead to argyria, which is the condition that Carlson and Stan Jones both had that turned them a blue. While argyria alone isn’t a serious health condition, it doesn’t go away when a person stops ingesting silver. Plus, too much silver can be fatal. [emphasis mine]

A November 17, 2023 news item on phys.org announced research from the Polish Academy of Sciences into improving antimicrobial activity, Note: A link has been removed,

Researchers at the Institute of Physical Chemistry of the Polish Academy of Sciences (IPC PAS) have demonstrated that green tea–silver nanoparticles as a powerful tool against pathogens such as bacteria and yeast. Their work is published in Nanoscale Advances.

An undated Institute of Physical Chemistry of the Polish Academy of Sciences (IPC PAS) press release (also published on EurekAlert and dated November 17, 2023), which originated the news item, describes this work, which is intended for medical applications, in more detail,

Once upon a time, people believed to be invincible against bacterial diseases, thanks to the antibiotics. Does this sound like a fairy tale? By all means! Nothing could be further from the truth. Despite widespread access to antibiotic therapy, many lives are lost due to pathogens invisible to the eye. The ability to develop drugs that can combat resistant strains of bacteria has not kept pace with the spread of resistance. So far, innovations to defeat antimicrobial-resistant strains of bacteria are in high demand. Recently, researchers at the Institute of Physical Chemistry of the Polish Academy of Sciences (IPC PAS) demonstrated green tea-silver nanoparticles as a powerful tool against pathogens such as bacteria and yeast. Their goal was to develop an efficient method to combat bacteria that are otherwise unaffected by antimicrobial agents, such as antibiotics.

Following the discovery of antibiotics, there came a change in the curse of mankind by accelerating the development of medicine and extending human life expectancy. Their successful implementation led to the rapid development of pharmacy, providing more and more drugs against many pathogens. Nevertheless, the overuse of antibiotics has led to the emergence of resistance to these compounds, becoming one of the biggest health threats worldwide. As a result, antibiotic resistance has emerged faster than the advancement of antibiotics . The appearance of new drugs on the horizon to combat these pathogens is a short-lasting spark. Even if we seem to be on the losing end, there is still a chance to defeat an invisible enemy.

This hitch was researched by the team of scientists from the IPC PAS under the supervision of Prof. Jan Paczesny, who proposed new nanoformulations for use against widespread and challenging pathogens such as ESKAPE bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) and other problematic yeast pathogens such as Candida auris or Cryptococcus neoformans. These microorganisms, treated with commercially available antibiotics, rapidly develop antibiotic resistance. Researchers chose ESKAPE as the target group since these pathogens lead to serious diseases, from sepsis to even cancer. How? This is where the story begins.

A few months ago, Paczesny’s team decided to try combining silver nanoparticles, which are known for their antimicrobial and antifungal properties, and tea extracts rich in polyphenols additionally possessing antioxidant properties. The concept was built to enhance broad-spectrum efficacy against pathogens using green hybrid silver nanoparticles (AgNPs), which are significantly more effective than all ingredients and even more effective than certain antibiotics. Why are these hybrid particles so special? In their work, three well-known tea varieties: black tea (B-Tea), green tea (G-Tea) and Pu-erh tea (R-Tea) were used as a capping agent, which acts as a stabilizer to protect the synthesized  particles from aggregation. In this way, the particles offer a high active surface area compared to other formulations. Additionally, such synthesis is eco-friendly for the use of natural ingredients during precipitation. The structures produced vary in shape and size from 34 to 65 nm, depending on the type of tea used during synthesis, and show different reactivity towards microorganisms.

Initially, silver nanoparticles produced in the presence of tea extracts (B-TeaNPs, G-TeaNPs and R-TeaNPs) were used to treat Gram-negative (E. coli) and Gram-positive (E. faecium) bacterial strains to test the effect on strains with different cell envelope morphologies. They looked at the interactions between the manufactured nanoparticles and the pathogens to determine efficacy, comparing the results with commercially available antibiotics. The ESKAPE pathogens were then tested according to a protocol for the most effective concentration and composition of the particles, revealing up to a 25% decrease in the number of bacterial cells in E. faecium and a 90% decrease in the case of E. cloacae. Interestingly, the green silver nanoparticles also showed antifungal activity, leading to an 80% decrease in the number of viable cells of C. auris and about a 90% decrease for C. neoformans.

The first author, Sada Raza claims “What is more, the size of nanoparticles is usually related to the cytotoxic effect of nanomaterials, with smaller particles being more cytotoxic. This should favor control AgNPs and R-TeaNPs over G-TeaNPs and B-TeaNPs in our experiments. This was not the case. In most experiments, C-AgNPs and R-TeaNPs showed the lowest antimicrobial efficacy. This is in line with other studies, which demonstrated that size is not a primary factor affecting the antimicrobial activity of AgNPs.

The antibacterial and antifungal properties of silver nanoparticles made with tea extracts are greater than those of silver nanoparticles alone due to their high content of phenolic compounds, isoflavonoids (especially catechins such as epigallocatechin (EGC) and epigallocatechin gallate (EGCG)). These combinations, using biologically active tea extracts and smaller amounts of silver nanoparticles, appear to be a potential way to combat a range of infections and even replace antibiotics in some applications.

“We established that silver nanoparticles synthesized with tea extracts have higher antibacterial properties than silver nanoparticles alone. Therefore, lower dosages of TeaNPs could be used (0.1 mg mL−1). We confirmed that in some cases, the synergistic effect of tea extracts and silver nanoparticles allowed for efficacy higher than that of antibiotics (ampicillin) when tested at the same concentrations (0.1 mg mL−1) and after a relatively short exposure time of three hours.” – remarks Mateusz Wdowiak, co-author of this work.

The researchers found that the antimicrobial hybrid nanoparticles resulted in a significant reduction in bacteria compared to antibiotics or compounds separately. Although not all bacteria were killed, this is a significant improvement that could aid the treatment of superbugs using much lower doses than other commercially available compounds. The amount of hybrid silver nanoparticles needed to overcome bacteria or fungal infections is extremely low, making them cost-effective, so the key to using them well is not only functionality, but also the low cost of application.

It is an approach that can also be adapted to combat other difficult-to-treat bacterial infections. The new nanoparticles developed by researchers at the IPC PAS could bring us one step closer to effectively killing deadly drug-resistant superbugs, providing an alternative to antibiotics against Gram-negative and Gram-positive bacteria. This study also shows how much more work there is to be done in this field. Compounds used separately were much less effective than the green hybrid.

In the future, the researchers’ main goal is to use nanoparticles in everyday life, starting with agricultural applications, replacing harmful compounds used in fields to overcome infestations in plants and bring us closer to organic farming. On a larger scale, the proposed material could also be used in biomedical applications, such as an additive for wound dressings to protect against Gram-negative and Gram-positive bacteria. They hope to use nanotechnology to develop more targeted treatments for drug-resistant superbugs.

Their work was published in Nanoscale Advances journal and was financed by the National Science Centre, Poland, within the SONATA BIS grant number 2017/26/E/ST4/00041 and Foundation for Polish Science from the European Regional Development Fund within the project POIR.04.04.00-00-14D6/18-00 ‘Hybrid sensor platforms for integrated photonic systems based on ceramic and polymer materials (HYPHa)’ (TEAM-NET program).

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

Enhancing the antimicrobial activity of silver nanoparticles against ESKAPE bacteria and emerging fungal pathogens by using tea extracts by Sada Raza, Mateusz Wdowiak, Mateusz Grotek, Witold Adamkiewicz, Kostiantyn Nikiforow, Pumza Mente, and Jan Paczesny. Nanoscale Adv., 2023,5, 5786-5798 DOI: https://doi.org/10.1039/D3NA00220A

This paper is licensed under a Creative Commons Attribution 3.0 Unported Licence. “You can use material from this article in other publications without requesting further permissions from the RSC [Royal Society of Chemistry], provided that the correct acknowledgement is given.” Or, consider it an open access paper.

Finally, this is not a recommendation not is it an endorsement for the ingestion of colloidal silver.

Simon Fraser University’s (SFU; Vancouver, Canada) Café Scientifique Winter/Spring 2024 events + a 2023 Nobel-themed lecture

There are three upcoming Simon Fraser University (SFU) Café Scientifique events (Zoom) and one upcoming Nobel=themed lecture (in person) according to a January 15, 2024 notice (received via email), Note: All the events are free,

Hello SFU Cafe Scientifique friends!

We are back with a brand new line up for our Cafe Scientifique discussion series.  Zoom invites will be sent closer to the event dates [emphasis mine].  We hope you can join us.

All event information and registration links on this page: https://www.sfu.ca/science/community.html

Café Scientifique: Why Do Babies Get Sick? A Systems Biology Approach to Developing Diagnostics and Therapeutics for Neonatal Sepsis. 

Tuesday, January 30, 5:00-6:30pm over Zoom 

Around the world five newborn babies die each second from life-threatening infections. Unfortunately there is no fast or easy way to tell which microbes are involved. Molecular Biology and Biochemistry assistant professor Amy Lee will share how we can use genomics and machine learning approaches to tackle this challenge.
Register here. https://events.sfu.ca/event/38235-cafe-scientifique-january-why-do-babies-get-sick?

Cafe Scientifique: From data to dollars: A journey through financial modelling
Tuesday, February 27, 5:00-6:30 pm over Zoom 

Financial modelling involves using mathematical and statistical techniques to understand future financial scenarios, helping individuals and businesses make informed decisions about their investments. Join Dr. Jean-François Bégin as he explores how these models can empower us to navigate the complexities of financial markets.

Register here: https://www.eventbrite.ca/e/763521010897

Cafe Scientifique: Overtraining and the Everyday Athlete
Tuesday, April 30, 5:00-6:30 pm over Zoom 

What happens when we train too hard, don’t take enough time to recover, or underfuel while exercising, and how that applies to both elite athletes and just your “everyday athlete.” Join Dr. Alexandra Coates from our Biomedical Physiology and Kinesiology Department in this interesting discussion.

Register here: https://www.eventbrite.ca/e/763521010897

Missed our last Café Scientifique talk [Decoding how life senses and responds to carbon dioxide gas] with Dustin King? [SFU Molecular Biology and Biochemistry Assistant Professor Dustin King’s Indigenous background is central to his work and relationship with the biochemical research he conducts. He brings Indigenous ways of knowing and a two-eye seeing approach to critical questions about humanity’s impact upon the natural world …] Watch it on YouTube: https://www.youtube.com/watch?v=xCHTSbF3RVs&list=PLTMt9gbqLurAMfSHQqVAHu7YbyOFq81Ix&index=10

The ‘2023 Nobel Prize Lectures’ being presented by SFU do not feature the 2023 winners but rather, SFU experts in the relevant field, from the January 15, 2024 SFU Café Scientifique notice (received via email),

BACK IN-PERSON AT THE SCIENCE WORLD THEATRE!

Location: Science World Theatre 1455 Quebec Street Vancouver, BC V6A 3Z7

NOBEL PRIZE LECTURES  

Wednesday, March 6, 2024 

6:30-7:30 pm Refreshments, 7:30-9:30 pm Lectures 

Celebrate the 2023 Nobel awardees in Chemistry, Physics, Physiology or Medicine!

SFU experts will explain Nobel laureates’ award-winning research and its significance to our everyday lives. 

Featured presenters are

*Mark Brockman from Molecular Biology and Biochemistry for the Nobel Prize in Medicine and Physiology;

*Byron Gates from Chemistry for the Nobel Prize in Chemistry; and

*Shawn Sederberg from the School of Engineering Science for the Nobel Prize in Physics.

Register here: https://www.eventbrite.ca/e/nobel-prize-lectures-tickets-773387301237

For anyone who has trouble remembering who and why the winners were awarded a 2023 Nobel Prize, here’s a nobleprize.org webpage devoted to the 2023 winners.

Reversing lower limb paralysis

This regenerative treatment is at a very early stage, which means the Swiss researchers have tried it on mice as you can see in the following video (runtime: 2 mins. 15 secs.). Towards the end of the video, researcher Grégoire Courtine cautions there are many hurdles before this could be used in humans, if ever,

A September 22, 2023 Ecole Polytechnique Fédérale de Lausanne (EPFL) press release (also on EurekAlert but published September 21, 2023) by Emmanuel Barraud, describes the work in more detail,

When the spinal cords of mice and humans are partially damaged, the initial paralysis is followed by the extensive, spontaneous recovery of motor function. However, after a complete spinal cord injury, this natural repair of the spinal cord doesn’t occur and there is no recovery. Meaningful recovery after severe injuries requires strategies that promote the regeneration of nerve fibers, but the requisite conditions for these strategies to successfully restore motor function have remained elusive.

“Five years ago, we demonstrated that nerve fibers can be regenerated across anatomically complete spinal cord injuries,” says Mark Anderson, a senior author of the study. “But we also realized this wasn’t enough to restore motor function, as the new fibers failed to connect to the right places on the other side of the lesion.” Anderson is the director of Central Nervous System Regeneration at .NeuroRestore and a scientist at the Wyss Center for Bio and Neuroengineering.

Working in tandem with peers at UCLA [University of California at Los Angeles] and Harvard Medical School, the scientists used state-of-the-art equipment at EPFL’s Campus Biotech facilities in Geneva to run in-depth analyses and identity which type of neuron is involved in natural spinal-cord repair after partial spinal cord injury. “Our observations using single-cell nuclear RNA sequencing not only exposed the specific axons that must regenerate, but also revealed that these axons must reconnect to their natural targets to restore motor function,” says Jordan Squair, the study’s first author. The team’s findings appear in the 22 September 2023 issue of Science.

Towards a combination of approaches

Their discovery informed the design of a multipronged gene therapy. The scientists activated growth programs in the identified neurons in mice to regenerate their nerve fibers, upregulated specific proteins to support the neurons’ growth through the lesion core, and administered guidance molecules to attract the regenerating nerve fibers to their natural targets below the injury. “We were inspired by nature when we designed a therapeutic strategy that replicates the spinal-cord repair mechanisms occurring spontaneously after partial injuries,” says Squair.

Mice with anatomically complete spinal cord injuries regained the ability to walk, exhibiting gait patterns that resembled those quantified in mice that resumed walking naturally after partial injuries. This observation revealed a previously unknown condition for regenerative therapies to be successful in restoring motor function after neurotrauma. “We expect that our gene therapy will act synergistically with our other procedures involving electrical stimulation of the spinal cord,” says Grégoire Courtine, a senior author of the study who also heads .NeuroRestore together with Jocelyne Bloch. “We believe a complete solution for treating spinal cord injury will require both approaches – gene therapy to regrow relevant nerve fibers, and spinal stimulation to maximize the ability of both these fibers and the spinal cord below the injury to produce movement.”

While many obstacles must still be overcome before this gene therapy can be applied in humans, the scientists have taken the first steps towards developing the technology necessary to achieve this feat in the years to come.

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

Recovery of walking after paralysis by regenerating characterized neurons to their natural target region by Jordan W. Squair, Marco Milano, Alexandra de Coucy, Matthieu Gautier, Michael A. Skinnider, Nicholas D. James, Newton Cho, Anna Lasne, Claudia Kathe,Thomas H. Hutson, Steven Ceto, Laetitia Baud, Katia Galan, Viviana Aureli, Achilleas Laskaratos, Quentin Barraud, Timothy J. Deming, Richie E. Kohman, Bernard L. Schneider, Zhigang He, Jocelyne Bloch, Michael V. Sofroniew, Gregoire Courtine, and Mark A. Anderson. Science 21 Sep 2023 Vol 381, Issue 6664 pp. 1338-1345 DOI: 10.1126/science.adi641

This paper is behind a paywall.

This March 25, 2015 posting, “Spinal cords, brains, implants, and remote control,” features some research from EPFL researchers whose names you might recognize from this posting’s research paper.

Mentioned in the press release, the Swiss research centre website for NeuroRestore is here.