Tag Archives: Karolinska Institutet

FrogHeart’s 2023 comes to an end as 2024 comes into view

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My personal theme for this last year (2023) and for the coming year was and is: catching up. On the plus side, my 2023 backlog (roughly six months) to be published was whittled down considerably. On the minus side, I start 2024 with a backlog of two to three months.

2023 on this blog had a lot in common with 2022 (see my December 31, 2022 posting), which may be due to what’s going on in the world of emerging science and technology or to my personal interests or possibly a bit of both. On to 2023 and a further blurring of boundaries:

Energy, computing and the environment

The argument against paper is that it uses up resources, it’s polluting, it’s affecting the environment, etc. Somehow the part where electricity which underpins so much of our ‘smart’ society does the same thing is left out of the discussion.

Neuromorphic (brainlike) computing and lower energy

Before launching into the stories about lowering energy usage, here’s an October 16, 2023 posting “The cost of building ChatGPT” that gives you some idea of the consequences of our insatiable desire for more computing and more ‘smart’ devices,

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In its latest environmental report, Microsoft disclosed that its global water consumption spiked 34% from 2021 to 2022 (to nearly 1.7 billion gallons , or more than 2,500 Olympic-sized swimming pools), a sharp increase compared to previous years that outside researchers tie to its AI research. [emphases mine]

“It’s fair to say the majority of the growth is due to AI,” including “its heavy investment in generative AI and partnership with OpenAI,” said Shaolei Ren, [emphasis mine] a researcher at the University of California, Riverside who has been trying to calculate the environmental impact of generative AI products such as ChatGPT.

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Why it matters: Microsoft’s five WDM [West Des Moines in Iowa] data centers — the “epicenter for advancing AI” — represent more than $5 billion in investments in the last 15 years.

Yes, but: They consumed as much as 11.5 million gallons of water a month for cooling, or about 6% of WDM’s total usage during peak summer usage during the last two years, according to information from West Des Moines Water Works.

The focus is AI but it doesn’t take long to realize that all computing has energy and environmental costs. I have more about Ren’s work and about water shortages in the “The cost of building ChatGPT” posting.

This next posting would usually be included with my other art/sci postings but it touches on the issues. My October 13, 2023 posting about Toronto’s Art/Sci Salon events, in particular, there’s the Streaming Carbon Footprint event (just scroll down to the appropriate subhead). For the interested, I also found this 2022 paper “The Carbon Footprint of Streaming Media:; Problems, Calculations, Solutions” co-authored by one of the artist/researchers (Laura U. Marks, philosopher and scholar of new media and film at Simon Fraser University) who presented at the Toronto event.

I’m late to the party; Thomas Daigle posted a January 2, 2020 article about energy use and our appetite for computing and ‘smart’ devices for the Canadian Broadcasting Corporation’s online news,

For those of us binge-watching TV shows, installing new smartphone apps or sharing family photos on social media over the holidays, it may seem like an abstract predicament.

The gigabytes of data we’re using — although invisible — come at a significant cost to the environment. Some experts say it rivals that of the airline industry. 

And as more smart devices rely on data to operate (think internet-connected refrigerators or self-driving cars), their electricity demands are set to skyrocket.

“We are using an immense amount of energy to drive this data revolution,” said Jane Kearns, an environment and technology expert at MaRS Discovery District, an innovation hub in Toronto.

“It has real implications for our climate.”

…

Some good news

Researchers are working on ways to lower the energy and environmental costs, here’s a sampling of 2023 posts with an emphasis on brainlike computing that attest to it,

If there’s an industry that can make neuromorphic computing and energy savings sexy, it’s the automotive indusry,

On the energy front,

Most people are familiar with nuclear fission and some its attendant issues. There is an alternative nuclear energy, fusion, which is considered ‘green’ or greener anyway. General Fusion is a local (Vancouver area) company focused on developing fusion energy, alongside competitors from all over the planet.

Part of what makes fusion energy attractive is that salt water or sea water can be used in its production and, according to that December posting, there are other applications for salt water power,

More encouraging developments in environmental science

Again, this is a selection. You’ll find a number of nano cellulose research projects and a couple of seaweed projects (seaweed research seems to be of increasing interest).

All by myself (neuromorphic engineering)

Neuromorphic computing is a subset of neuromorphic engineering and I stumbled across an article that outlines the similarities and differences. My ‘summary’ of the main points and a link to the original article can be found here,

Oops! I did it again. More AI panic

I included an overview of the various ‘recent’ panics (in my May 25, 2023 posting below) along with a few other posts about concerning developments but it’s not all doom and gloom..

Governments have realized that regulation might be a good idea. The European Union has a n AI act, the UK held an AI Safety Summit in November 2023, the US has been discussing AI regulation with its various hearings, and there’s impending legislation in Canada (see professor and lawyer Michael Geist’s blog for more).

A long time coming, a nanomedicine comeuppance

Paolo Macchiarini is now infamous for his untested, dangerous approach to medicine. Like a lot of people, I was fooled too as you can see in my August 2, 2011 posting, “Body parts nano style,”

In early July 2011, there were reports of a new kind of transplant involving a body part made of a biocomposite. Andemariam Teklesenbet Beyene underwent a trachea transplant that required an artificial windpipe crafted by UK experts then flown to Sweden where Beyene’s stem cells were used to coat the windpipe before being transplanted into his body.

It is an extraordinary story not least because Beyene, a patient in a Swedish hospital planning to return to Eritrea after his PhD studies in Iceland, illustrates the international cooperation that made the transplant possible.

The scaffolding material for the artificial windpipe was developed by Professor Alex Seifalian at the University College London in a landmark piece of nanotechnology-enabled tissue engineering. …

Five years later I stumbled across problems with Macchiarini’s work as outlined in my April 19, 2016 posting, “Macchiarini controversy and synthetic trachea transplants (part 1 of 2)” and my other April 19, 2016 posting, “Macchiarini controversy and synthetic trachea transplants (part 2 of 2)“.

This year, Gretchen Vogel (whose work was featured in my 2016 posts) has written a June 21, 2023 update about the Macchiarini affair for Science magazine, Note: Links have been removed,

Surgeon Paolo Macchiarini, who was once hailed as a pioneer of stem cell medicine, was found guilty of gross assault against three of his patients today and sentenced to 2 years and 6 months in prison by an appeals court in Stockholm. The ruling comes a year after a Swedish district court found Macchiarini guilty of bodily harm in two of the cases and gave him a suspended sentence. After both the prosecution and Macchiarini appealed that ruling, the Svea Court of Appeal heard the case in April and May. Today’s ruling from the five-judge panel is largely a win for the prosecution—it had asked for a 5-year sentence whereas Macchiarini’s lawyer urged the appeals court to acquit him of all charges.

Macchiarini performed experimental surgeries on the three patients in 2011 and 2012 while working at the renowned Karolinska Institute. He implanted synthetic windpipes seeded with stem cells from the patients’ own bone marrow, with the hope the cells would multiply over time and provide an enduring replacement. All three patients died when the implants failed. One patient died suddenly when the implant caused massive bleeding just 4 months after it was implanted; the two others survived for 2.5 and nearly 5 years, respectively, but suffered painful and debilitating complications before their deaths.

In the ruling released today, the appeals judges disagreed with the district court’s decision that the first two patients were treated under “emergency” conditions. Both patients could have survived for a significant length of time without the surgeries, they said. The third case was an “emergency,” the court ruled, but the treatment was still indefensible because by then Macchiarini was well aware of the problems with the technique. (One patient had already died and the other had suffered severe complications.)

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A fictionalized tv series ( part of the Dr. Death anthology series) based on Macchiarini’s deceptions and a Dr. Death documentary are being broadcast/streamed in the US during January 2024. These come on the heels of a November 2023 Macchiarini documentary also broadcast/streamed on US television.

Dr. Death (anthology), based on the previews I’ve seen, is heavily US-centric, which is to be expected since Adam Ciralsky is involved in the production. Ciralsky wrote an exposé about Macchiarini for Vanity Fair published in 2016 (also featured in my 2016 postings). From a December 20, 2023 article by Julie Miller for Vanity Fair, Note: A link has been removed,

Seven years ago [2016], world-renowned surgeon Paolo Macchiarini was the subject of an ongoing Vanity Fair investigation. He had seduced award-winning NBC producer Benita Alexander while she was making a special about him, proposed, and promised her a wedding officiated by Pope Francis and attended by political A-listers. It was only after her designer wedding gown was made that Alexander learned Macchiarini was still married to his wife, and seemingly had no association with the famous names on their guest list.

Vanity Fair contributor Adam Ciralsky was in the midst of reporting the story for this magazine in the fall of 2015 when he turned to Dr. Ronald Schouten, a Harvard psychiatry professor. Ciralsky sought expert insight into the kind of fabulist who would invent and engage in such an audacious lie.

“I laid out the story to him, and he said, ‘Anybody who does this in their private life engages in the same conduct in their professional life,” recalls Ciralsky, in a phone call with Vanity Fair. “I think you ought to take a hard look at his CVs.”

That was the turning point in the story for Ciralsky, a former CIA lawyer who soon learned that Macchiarini was more dangerous as a surgeon than a suitor. …

Here’s a link to Ciralsky’s original article, which I described this way, from my April 19, 2016 posting (part 2 of the Macchiarini controversy),

For some bizarre frosting on this disturbing cake (see part 1 of the Macchiarini controversy and synthetic trachea transplants for the medical science aspects), a January 5, 2016 Vanity Fair article by Adam Ciralsky documents Macchiarini’s courtship of an NBC ([US] National Broadcasting Corporation) news producer who was preparing a documentary about him and his work.

[from Ciralsky’s article]

“Macchiarini, 57, is a magnet for superlatives. He is commonly referred to as “world-renowned” and a “super-surgeon.” He is credited with medical miracles, including the world’s first synthetic organ transplant, which involved fashioning a trachea, or windpipe, out of plastic and then coating it with a patient’s own stem cells. That feat, in 2011, appeared to solve two of medicine’s more intractable problems—organ rejection and the lack of donor organs—and brought with it major media exposure for Macchiarini and his employer, Stockholm’s Karolinska Institute, home of the Nobel Prize in Physiology or Medicine. Macchiarini was now planning another first: a synthetic-trachea transplant on a child, a two-year-old Korean-Canadian girl named Hannah Warren, who had spent her entire life in a Seoul hospital. … “

Other players in the Macchiarini story

Pierre Delaere, a trachea expert and professor of head and neck surgery at KU Leuven (a university in Belgium) was one of the first to draw attention to Macchiarini’s dangerous and unethical practices. To give you an idea of how difficult it was to get attention for this issue, there’s a September 1, 2017 article by John Rasko and Carl Power for the Guardian illustrating the issue. Here’s what they had to say about Delaere and other early critics of the work, Note: Links have been removed,

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Delaere was one of the earliest and harshest critics of Macchiarini’s engineered airways. Reports of their success always seemed like “hot air” to him. He could see no real evidence that the windpipe scaffolds were becoming living, functioning airways – in which case, they were destined to fail. The only question was how long it would take – weeks, months or a few years.

Delaere’s damning criticisms appeared in major medical journals, including the Lancet, but weren’t taken seriously by Karolinska’s leadership. Nor did they impress the institute’s ethics council when Delaere lodged a formal complaint. [emphases mine]

Support for Macchiarini remained strong, even as his patients began to die. In part, this is because the field of windpipe repair is a niche area. Few people at Karolinska, especially among those in power, knew enough about it to appreciate Delaere’s claims. Also, in such a highly competitive environment, people are keen to show allegiance to their superiors and wary of criticising them. The official report into the matter dubbed this the “bandwagon effect”.

With Macchiarini’s exploits endorsed by management and breathlessly reported in the media, it was all too easy to jump on that bandwagon.

And difficult to jump off. In early 2014, four Karolinska doctors defied the reigning culture of silence [emphasis mine] by complaining about Macchiarini. In their view, he was grossly misrepresenting his results and the health of his patients. An independent investigator agreed. But the vice-chancellor of Karolinska Institute, Anders Hamsten, wasn’t bound by this judgement. He officially cleared Macchiarini of scientific misconduct, allowing merely that he’d sometimes acted “without due care”.

For their efforts, the whistleblowers were punished. [emphasis mine] When Macchiarini accused one of them, Karl-Henrik Grinnemo, of stealing his work in a grant application, Hamsten found him guilty. As Grinnemo recalls, it nearly destroyed his career: “I didn’t receive any new grants. No one wanted to collaborate with me. We were doing good research, but it didn’t matter … I thought I was going to lose my lab, my staff – everything.”

This went on for three years until, just recently [2017], Grinnemo was cleared of all wrongdoing.

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It is fitting that Macchiarini’s career unravelled at the Karolinska Institute. As the home of the Nobel prize in physiology or medicine, one of its ambitions is to create scientific celebrities. Every year, it gives science a show-business makeover, picking out from the mass of medical researchers those individuals deserving of superstardom. The idea is that scientific progress is driven by the genius of a few.

It’s a problematic idea with unfortunate side effects. A genius is a revolutionary by definition, a risk-taker and a law-breaker. Wasn’t something of this idea behind the special treatment Karolinska gave Macchiarini? Surely, he got away with so much because he was considered an exception to the rules with more than a whiff of the Nobel about him. At any rate, some of his most powerful friends were themselves Nobel judges until, with his fall from grace, they fell too.

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The September 1, 2017 article by Rasko and Power is worth the read if you have the interest and the time. And, Delaere has written up a comprehensive analysis, which includes basic information about tracheas and more, “The Biggest Lie in Medical History” 2020, PDF, 164 pp., Creative Commons Licence).

I also want to mention Leonid Schneider, science journalist and molecular cell biologist, whose work the Macchiarini scandal on his ‘For Better Science’ website was also featured in my 2016 pieces. Schneider’s site has a page titled, ‘Macchiarini’s trachea transplant patients: the full list‘ started in 2017 and which he continues to update with new information about the patients. The latest update was made on December 20, 2023.

Promising nanomedicine research but no promises and a caveat

Most of the research mentioned here is still in the laboratory. i don’t often come across work that has made its way to clinical trials since the focus of this blog is emerging science and technology,

*If you’re interested in the business of neurotechnology, the July 17, 2023 posting highlights a very good UNESCO report on the topic.

Funky music (sound and noise)

I have couple of stories about using sound for wound healing, bioinspiration for soundproofing applications, detecting seismic activity, more data sonification, etc.

Same old, same old CRISPR

2023 was relatively quiet (no panics) where CRISPR developments are concerned but still quite active.

Art/Sci: a pretty active year

I didn’t realize how active the year was art/sciwise including events and other projects until I reviewed this year’s postings. This is a selection from 2023 but there’s a lot more on the blog, just use the search term, “art/sci,” or “art/science,” or “sciart.”

While I often feature events and projects from these groups (e.g., June 2, 2023 posting, “Metacreation Lab’s greatest hits of Summer 2023“), it’s possible for me to miss a few. So, you can check out Toronto’s Art/Sci Salon’s website (strong focus on visual art) and Simon Fraser University’s Metacreation Lab for Creative Artificial Intelligence website (strong focus on music).

My selection of this year’s postings is more heavily weighted to the ‘writing’ end of things.

Boundaries: life/nonlife

Last year I subtitled this section, ‘Aliens on earth: machinic biology and/or biological machinery?” Here’s this year’s selection,

Canada’s 2023 budget … military

2023 featured an unusual budget where military expenditures were going to be increased, something which could have implications for our science and technology research.

Then things changed as Murray Brewster’s November 21, 2023 article for the Canadian Broadcasting Corporation’s (CBC) news online website comments, Note: A link has been removed,

There was a revelatory moment on the weekend as Defence Minister Bill Blair attempted to bridge the gap between rhetoric and reality in the Liberal government’s spending plans for his department and the Canadian military.

Asked about an anticipated (and long overdue) update to the country’s defence policy (supposedly made urgent two years ago by Russia’s full-on invasion of Ukraine), Blair acknowledged that the reset is now being viewed through a fiscal lens.

“We said we’re going to bring forward a new defence policy update. We’ve been working through that,” Blair told CBC’s Rosemary Barton Live on Sunday.

“The current fiscal environment that the country faces itself does require (that) that defence policy update … recognize (the) fiscal challenges. And so it’ll be part of … our future budget processes.”

…

One policy goal of the existing defence plan, Strong, Secure and Engaged, was to require that the military be able to concurrently deliver “two sustained deployments of 500 [to] 1,500 personnel in two different theaters of operation, including one as a lead nation.”

In a footnote, the recent estimates said the Canadian military is “currently unable to conduct multiple operations concurrently per the requirements laid out in the 2017 Defence Policy. Readiness of CAF force elements has continued to decrease over the course of the last year, aggravated by decreasing number of personnel and issues with equipment and vehicles.”

Some analysts say they believe that even if the federal government hits its overall budget reduction targets, what has been taken away from defence — and what’s about to be taken away — won’t be coming back, the minister’s public assurances notwithstanding.

…

10 years: Graphene Flagship Project and Human Brain Project

“Graphene and Human Brain Project win biggest research award in history (& this is the 2000th post)” on January 28, 2013 was how I announced the results of what had been a a European Union (EU) competition that stretched out over several years and many stages as projects were evaluated and fell to the wayside or were allowed onto the next stage. The two finalists received €1B each to be paid out over ten years.

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Future or not

As you can see, there was plenty of interesting stuff going on in 2023 but no watershed moments in the areas I follow. (Please do let me know in the Comments should you disagree with this or any other part of this posting.) Nanotechnology seems less and less an emerging science/technology in itself and more like a foundational element of our science and technology sectors. On that note, you may find my upcoming (in 2024) post about a report concerning the economic impact of its National Nanotechnology Initiative (NNI) from 2002 to 2022 of interest.

Following on the commercialization theme, I have noticed an increase of interest in commercializing brain and brainlike engineering technologies, as well as, more discussion about ethics.

Colonizing the brain?

UNESCO held events such as, this noted in my July 17, 2023 posting, “Unveiling the Neurotechnology Landscape: Scientific Advancements, Innovations and Major Trends—a UNESCO report” and this noted in my July 7, 2023 posting “Global dialogue on the ethics of neurotechnology on July 13, 2023 led by UNESCO.” An August 21, 2023 posting, “Ethical nanobiotechnology” adds to the discussion.

Meanwhile, Australia has been producing some very interesting mind/robot research, my June 13, 2023 posting, “Mind-controlled robots based on graphene: an Australian research story.” I have more of this kind of research (mind control or mind reading) from Australia to be published in early 2024. The Australians are not alone, there’s also this April 12, 2023 posting, “Mind-reading prosthetic limbs” from Germany.

My May 12, 2023 posting, “Virtual panel discussion: Canadian Strategies for Responsible Neurotechnology Innovation on May 16, 2023” shows Canada is entering the discussion. Unfortunately, the Canadian Science Policy Centre (CSPC), which held the event, has not posted a video online even though they have a youtube channel featuring other of their events.

As for neurmorphic engineering, China has produced a roadmap for its research in this area as noted in my March 20, 2023 posting, “A nontraditional artificial synaptic device and roadmap for Chinese research into neuromorphic devices.”

Quantum anybody?

I haven’t singled it out in this end-of-year posting but there is a great deal of interest in quantum computer both here in Canada and elsewhere. There is a 2023 report from the Council of Canadian Academies on the topic of quantum computing in Canada, which I hope to comment on soon.

Final words

I have a shout out for the Canadian Science Policy Centre, which celebrated its 15th anniversary in 2023. Congratulations!

For everyone, I wish peace on earth and all the best for you and yours in 2024!

Bioelectronics: creating components that speak the body’s own language

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This is work is still in its early stages but the idea that the body could be stimulated to release more of its own pain relievers is exciting. From a Nov. 2, 2016 news item on ScienceDaily,

With a microfabricated ion pump built from organic electronic components, ions can be sent to nerve or muscle cells at the speed of the nervous system and with a precision of a single cell. “Now we can start to develop components that speak the body’s own language,” says Daniel Simon, head of bioelectronics research at the Laboratory of Organic Electronics, Linköping University, Campus Norrköping.

A Nov. 2, 2016 Linköping University press release (also on EurekAlert), which originated the news item, discusses the research in more detail,

Our nerve and muscle cells send signals to each other using ions and molecules. Certain substances, such as the neurotransmitter GABA (gamma aminobutyric acid), are important signal substances throughout the central nervous system. Eighteen months ago, researchers at the Laboratory of Organic Electronics demonstrated an ion pump which researchers at the Karolinska Institutet could use to reduce the sensation of pain in awake, freely-moving rats. The ion pump delivered GABA directly to the rat´s spinal cord. The news that researchers could deliver the body’s own neurotransmitters was published in Science Advances and garnered intense interest all over the world.

The research group at the Laboratory of Organic Electronics has now achieved another major advance and developed a significantly smaller and more rapid ion pump that transmits signals nearly as rapidly as the cells themselves, and with a precision on the scale of an individual cell. …

“Our skilled doctoral students, Amanda Jonsson and Theresia Arbring Sjöström, have succeeded with the last important part of the puzzle in the development of the ion pump. When a signal passes between two synapses it takes 1-10 milliseconds, and we are now very close to the nervous system’s own speed,” says Magnus Berggren, professor of organic electronics and director of the Laboratory of Organic Electronics.

“We conclude that we have produced artificial nerves that can communicate seamlessly with the nervous system. After more than 10 years’ research we have finally got all the parts of the puzzle in place,” he says.

Amanda Jonsson, who together with Theresia Arbring Sjöström is principal author of the article in Science Advances, has developed the pain-alleviating ion pump as part of her doctoral studies. She proudly presents a glass disk with many of the new miniaturized ion pumps. Some pumps have only a single outlet, but others have six tiny point outlets.

“We can make them with several outlets, it’s just as easy as making one. And all of the outlets can be individually controlled. Previously we could only transport ions horizontally and from all outputs at the same time. Now, however, we can deliver the ions vertically, which makes the distance they have to be transported as short as a micrometre,” she explains.

All of the outputs of the ion pump can also be rapidly switched on or off with the aid of micrometre-sized ion diodes.

“The ions are released rapidly by an electrical signal, in the same way that the neurotransmitter is released in a synapse,” says Theresia Arbring Sjöström.

Organic electronic components have a major advantage here: they can conduct both ions and electricity. In this case, the material PEDOT:PSS enables the electrical signals to be converted to chemical signals that the body understands.

The ion diode has recently been developed, as has the material that forms the basis of the new rapid ion pump.

“The new material makes it possible to build with a precision and reliability not possible in previous versions of the ion pump,” says Daniel Simon.

The new ion pump has so far only been tested in the laboratory. The next step will be to test it with live cells and the researchers hope eventually to, for example alleviate pain, stop epileptic seizures, and reduce the symptoms of Parkinsons disease, using exactly the required dose at exactly the affected cells. Communication using the cell´s own language, and the cell´s own speed.

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

Chemical delivery array with millisecond neurotransmitter release by Amanda Jonsson, Theresia Arbring Sjöström, Klas Tybrandt, Magnus Berggren, and Daniel T. Simon. Science Advances  02 Nov 2016: Vol. 2, no. 11, e1601340 DOI: 10.1126/sciadv.1601340

This paper is open access.

Researchers at Karolinska Institute (Sweden) build an artificial neuron

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Unlike my post earlier today (June 26, 2015) about BrainChip, this is not about neuromorphic engineering (artificial brain), although I imagine this new research from the Karolinska Institute (Institutet) will be of some interest to that community. This research was done in the interest of developing* therapeutic interventions for brain diseases. One aspect of this news item/press release I find particularly interesting is the insistence that “no living parts” were used to create the artificial neuron,

A June 24, 2015 news item on ScienceDaily describes what the artificial neuron can do,

Scientists have managed to build a fully functional neuron by using organic bioelectronics. This artificial neuron contain [sic] no ‘living’ parts, but is capable of mimicking the function of a human nerve cell and communicate in the same way as our own neurons do. [emphasis mine]

A June 24, 2015 Karolinska Institute press release (also on EurekAlert), which originated the news item, describes how neurons communicate in the brain, standard techniques for stimulating neuronal cells, and the scientists’ work on a technique to improve stimulation,

Neurons are isolated from each other and communicate with the help of chemical signals, commonly called neurotransmitters or signal substances. Inside a neuron, these chemical signals are converted to an electrical action potential, which travels along the axon of the neuron until it reaches the end. Here at the synapse, the electrical signal is converted to the release of chemical signals, which via diffusion can relay the signal to the next nerve cell.

To date, the primary technique for neuronal stimulation in human cells is based on electrical stimulation. However, scientists at the Swedish Medical Nanoscience Centre (SMNC) at Karolinska Institutet in collaboration with collegues at Linköping University, have now created an organic bioelectronic device that is capable of receiving chemical signals, which it can then relay to human cells.

“Our artificial neuron is made of conductive polymers and it functions like a human neuron,” says lead investigator Agneta Richter-Dahlfors, professor of cellular microbiology. “The sensing component of the artificial neuron senses a change in chemical signals in one dish, and translates this into an electrical signal. This electrical signal is next translated into the release of the neurotransmitter acetylcholine in a second dish, whose effect on living human cells can be monitored.”

The research team hope that their innovation, presented in the journal Biosensors & Bioelectronics, will improve treatments for neurologial disorders which currently rely on traditional electrical stimulation. The new technique makes it possible to stimulate neurons based on specific chemical signals received from different parts of the body. In the future, this may help physicians to bypass damaged nerve cells and restore neural function.

“Next, we would like to miniaturize this device to enable implantation into the human body,” says Agneta Richer-Dahlfors. “We foresee that in the future, by adding the concept of wireless communication, the biosensor could be placed in one part of the body, and trigger release of neurotransmitters at distant locations. Using such auto-regulated sensing and delivery, or possibly a remote control, new and exciting opportunities for future research and treatment of neurological disorders can be envisaged.”

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

An organic electronic biomimetic neuron enables auto-regulated neuromodulation by Daniel T. Simon, Karin C. Larsson, David Nilsson, Gustav Burström, b, Dagmar Galter, Magnus Berggren, and Agneta Richter-Dahlfors. Biosensors and Bioelectronics Volume 71, 15 September 2015, Pages 359–364         doi:10.1016/j.bios.2015.04.058

This paper is behind a paywall.

As to anyone (other than myself) who may be curious about exactly what they used (other than “living parts”) to create an artificial neuron, there’s the paper’s abstract,

Current therapies for neurological disorders are based on traditional medication and electric stimulation. Here, we present an organic electronic biomimetic neuron, with the capacity to precisely intervene with the underlying malfunctioning signalling pathway using endogenous substances. The fundamental function of neurons, defined as chemical-to-electrical-to-chemical signal transduction, is achieved by connecting enzyme-based amperometric biosensors and organic electronic ion pumps. Selective biosensors transduce chemical signals into an electric current, which regulates electrophoretic delivery of chemical substances without necessitating liquid flow. Biosensors detected neurotransmitters in physiologically relevant ranges of 5–80 µM, showing linear response above 20 µm with approx. 0.1 nA/µM slope. When exceeding defined threshold concentrations, biosensor output signals, connected via custom hardware/software, activated local or distant neurotransmitter delivery from the organic electronic ion pump. Changes of 20 µM glutamate or acetylcholine triggered diffusive delivery of acetylcholine, which activated cells via receptor-mediated signalling. This was observed in real-time by single-cell ratiometric Ca2+ imaging. The results demonstrate the potential of the organic electronic biomimetic neuron in therapies involving long-range neuronal signalling by mimicking the function of projection neurons. Alternatively, conversion of glutamate-induced descending neuromuscular signals into acetylcholine-mediated muscular activation signals may be obtained, applicable for bridging injured sites and active prosthetics.

While it’s true neither are “living parts,” I believe both enzymes and organic electronic ion pumps can be found in biological organisms. The insistence on ‘nonliving’ in the press release suggests that scientists in Europe, if nowhere else, are still quite concerned about any hint that they are working on genetically modified organisms (GMO). It’s ironic when you consider that people blithely use enzyme-based cleaning and beauty products but one can appreciate the* scientists’ caution.

* ‘develop’ changed to ‘developing’ and ‘the’ added on July 3, 2015.

Trachea transplants: an update

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I got curious the other day about trachea transplants, a topic I first wrote about one an Aug. 22, 2011 posting featuring Andemariam Teklesenbet Beyene and wondered how things had worked out for him. For anyone who doesn’t know the story, ,

In early July 2011, there were reports of a new kind of transplant involving a body part made of a biocomposite. Andemariam Teklesenbet Beyene underwent a trachea transplant that required an artificial windpipe crafted by UK experts then flown to Sweden where Beyene’s stem cells were used to coat the windpipe before being transplanted into his body.

It is an extraordinary story not least because Beyene, a patient in a Swedish hospital planning to return to Eritrea after his PhD studies in Iceland, illustrates the international cooperation that made the transplant possible.

The scaffolding material for the artificial windpipe was developed by Professor Alex Seifalian at the University College London in a landmark piece of nanotechnology-enabled tissue engineering. Tim Harper in his July 25, 2011 posting provides more details about the scaffolding,

A team led by Professor Alexander Seifalian (UCL Division of Surgery & Interventional Science; professor of nanotechnology and regenerative medicine at University College London, UK), whose laboratories are headquartered at the Royal Free Hospital, created a glass mold of the patient’s trachea from X-ray computed tomography (CT) scans of the patient. In CT, digital geometry processing is employed to generate a 3D image of the inside of an object from a large series of 2D X-ray images taken around one single axis of rotation.

Then, they manufactured a full size y-shaped trachea scaffold at Professor Seifalian’s laboratories. The scaffold of the trachea was built using a novel nanocomposite polymer developed and patented by Professor Seifalian. Professor Seifalian worked together with Professor Paolo Macchiarini at Karolinska Institutet, Stockholm, Sweden (who also holds an Honorary appointment at UCL).

…

What I didn’t realize in 2011 was there had been some earlier transplants as Gretchen Vogel writes in her April 19, 2013  article (Trachea Transplants Test the Limits) which summarizes and critiques the work* on synthesized tracheas to date for Science magazine (the article is behind a a paywall),

More than a dozen ill people have received a bioengineered trachea seeded with stem cells during the past 5 years, but outcomes are mixed, and critics say the treatment may not do what its developers claim.

…

Although at first glance the trachea might seem like a simple tube, its thin but cartilage-reinforced walls must stand up to near-constant use as a person breathes, clears his throat, or coughs. Any transplant, therefore, has to be strong enough to withstand such pressures without collapsing. But a rigid prosthesis can rub against and damage the adjacent major blood vessels in the upper part of the chest, leaving a patient at risk for a fatal hemorrhage. At the same time, the natural blood supply for the trachea’s tissues is intricate, with vessels too small for surgeons to easily reconnect during a transplant operation. And because it is exposed to inhaled air, the wound between the implant and the remaining airway is especially vulnerable to infection.

Surgeons have tried for years to find ways around these challenges, without much success. When Castillo (Claudia Castillo,  first patient to receive a trachea transplant using her own stem cells) was hospitalized in Barcelona in March 2008, Macchiarini [Paolo Macchiarini], who was then at the University of Barcelona’s Hospital Clínic, and Birchall [Martin Birchall], then at the University of Bristol in the United Kingdom, had experimented with bioengineered transplants in pigs. They would take a trachea from a pig and remove its living cells to create a so-called decellularized scaffold. They seeded this with cells from the recipient pig: bone marrow cells on the outer layer, thought to help form new cartilage, and epithelial cells on the inside, which they hoped would regrow the trachea’s lining. They allowed the cells to grow on the scaffold for several days in a bioreactor designed to provide different conditions for the two types of cells. They hoped that the decellularized scaffold would not require immunosuppressive drugs to prevent its rejection and that the seeded cells would take over the removed cells’ roles, ultimately forming a living organ.

The main difference between the 2008 Castillo operation and the 2011 Teklesenbet Beyene,operation is the scaffolding. For Castillo, they used a cadaverous** trachea where living cells were removed to create a ‘decellularized’ scaffold. For Teklesenbet Beyene, they used a nanocomposite** polymer. According to Vogel, 14 people have had the operation using either the decellularized or the nanocomposite composite polymer as the base for a new trachea. There have been some problems and deaths although Castillo who is still alive did not respond to any of Vogel’s requests for a comment . As for Teklesenbet Beyene (from the article),

His current doctor, Tomas Gudbjartsson of Landspitali University Hospital in Reykjavik, tells Science that Beyene has had several stents, but is healthy enough that he was able to complete his studies last year [2012]. The researchers have mentioned other patients in passing in several papers, but no formal reports have been published about their health, and Science has not been able to independently verify the current status of all the patients.

Both Birchall and Macchiarini have received grants for clinical trials,

In March [2013?[, Birchall received a £2.8 million ($4.3 million) grant from the United Kingdom’s Medical Research Council to conduct a trial of decellularized and stem cell–seeded upper trachea and larynx, with roughly 10 patients. Macchiarini has already completed two transplants in Russia as part of a clinical trial—funded with a $6 million grant from the Russian government—that he says should eventually enroll 20 or 25 patients. “We were allowed to do this type of transplantation only in extreme cases,” he says. “The clinical study for the first time gives us a chance to include patients who are not in such critical shape.”

Macchiarini is also the lead investigator on a 5-year, €4 million ($5.2 million) grant from the European Union to begin a clinical trial using decellularized tracheas and further develop the polymer scaffolds in large animal models. That project may need to be reorganized, however, following a legal dispute last year in Italy, where the transplants were supposed to take place—Macchiarini had a part-time position at Careggi Hospital in Florence. In September, however, Italy’s financial police accused him of attempted extortion, and briefly placed him under house arrest, for allegedly telling a patient that he could receive treatment in Germany for €150,000. Macchiarini and his lawyer say that he was simply informing the patient of possible options, not demanding payment. The main charges were soon dropped, but Macchiarini says that the charges stemmed from academic politics in Tuscany and he has severed ties with the hospital and university there. “There is no way to go back there.”

That last bit (in the excerpt) about academic politics in Tuscany seems downright Machiavellian (Wikipedia essay on Machiavelli here).

Getting back to the trachea transplants, there seems to be a major difference of opinion. While the researchers Macchiarini and Birchall have opted for human clinical trials other experts are suggesting that animal trials should be the next step for this research. I recommend reading Vogel’s article so you can fully appreciate the debate.

*’which a summary and critique of the work’ changed to ‘which summarizes and critiques the work’ for grammatical correctness on April 8, 2016.

**’pig trachea’ changed to ‘cadaverous trachea’ and ‘nanocompostie’ changed to ‘nanocomposite’ on April 19, 2016.

More on synthetic windpipe; Swedes and Italians talk about nanoscience and medicine

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There was a Swedish-Italian workshop on nanoscience and medical technology held in Stockholm, Sweden, Sept. 29 and 30, 2011. It rates a mention here largely because there’s some additional information about the synthetic windpipe transplant that took place in June 2011 in Sweden. From the Oct. 14, 2011 news item on Nanowerk,

A very important session was devoted to “tissue engineering”, i.e. the creation of artificial tissues and organs to replace diseased or damaged ones, thus reducing the need for human organs from donors for transplantation, whose availability is always difficult to predict. A “keynote lecturer”, in this field was held by Prof. Paolo Macchiarini, who recently joined the Karolinska Institute in Stockholm (the Institute that awards the Nobel Prize in Medicine each year).

Prof. Macchiarini presented the results of his recent surgery works, performed at the Karolinska, where for the first time a synthetic trachea (windpipe) made of porous nanocomposites was transplanted into a human patient. This was the base for the trachea reconstruction using stem cells from the patient himself, thus eliminating any possible problem of rejection. The artificial structure was designed to dissolve in a few months, leaving a totally natural organ. [emphasis mine] It is clear that this could be a first step in a revolution in regenerative medicine, reducing the need for conventional transplants, but it is also clear that the Prof. Macchiarini was able to perform this action thanks to the collaboration of experts in nanotechnology for the design of the scaffold, bioreactors for the growth of stem cells and biological tissues and dedicated infrastructure in Stockholm.

I must have missed it when the event (trachea transplant) was first made public (mentioned in my Aug. 2, 2011 posting) but I never realized the biocomposite was meant to dissolve.

Here’s a little more about the workshop, from the news item,

During the workshop, 18 Swedish and 18 Italian experts offered a comprehensive overview of the most prominent activities in the two Countries in several fields: bio-sensors, bio-electronics, contrast media for imaging and bio-analysis, nanoparticles for drug delivery eventually combined with diagnosis possibilities (known in the field as “theranostics”).

Several companies from both countries, including Bracco, Finceramica and Colorbbia from Italy as well as AstraZeneca and Spago Imaging from Sweden, presented their recent results in the field and gave a clear overview of the potential impact of nanotechnology in improving existing products as well as generating new solutions for the grand challenges that medicine is facing.

There are more details in the news item and at the Italian Embassy in Sweden’s Office of the Scientific Attaché in Sweden, Norway and Iceland workshop page.

Body parts nano style

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In early July 2011, there were reports of a new kind of transplant involving a body part made of a biocomposite. Andemariam Teklesenbet Beyene underwent a trachea transplant that required an artificial windpipe crafted by UK experts then flown to Sweden where Beyene’s stem cells were used to coat the windpipe before being transplanted into his body.

It is an extraordinary story not least because Beyene, a patient in a Swedish hospital planning to return to Eritrea after his PhD studies in Iceland, illustrates the international cooperation that made the transplant possible.

The scaffolding material for the artificial windpipe was developed by Professor Alex Seifalian at the University College London in a landmark piece of nanotechnology-enabled tissue engineering. Tim Harper in his July 25, 2011 posting provides more details about the scaffolding,

A team led by Professor Alexander Seifalian (UCL Division of Surgery & Interventional Science; professor of nanotechnology and regenerative medicine at University College London, UK), whose laboratories are headquartered at the Royal Free Hospital, created a glass mold of the patient’s trachea from X-ray computed tomography (CT) scans of the patient. In CT, digital geometry processing is employed to generate a 3D image of the inside of an object from a large series of 2D X-ray images taken around one single axis of rotation.

Then, they manufactured a full size y-shaped trachea scaffold at Professor Seifalian’s laboratories. The scaffold of the trachea was built using a novel nanocomposite polymer developed and patented by Professor Seifalian. Professor Seifalian worked together with Professor Paolo Macchiarini at Karolinska Institutet, Stockholm, Sweden (who also holds an Honorary appointment at UCL).

Professor Seifalian and his team used a porous novel nanocomposite polymer to build the y-shaped trachea scaffold. The pores were millions of little holes, providing this way a place for the patient’s stem cells to grow roots. The team cut strips of the novel nanocomposite polymer and wrapped them around the glass mold creating this way the cartilage rings that conferred structural strength to the trachea.

After the scaffold construct was finished, it was taken to Karolinska Institutet where the patient’s stem cells were seeded by Professor Macchiarini’s team.

Harper goes on to provide more details and insight into what makes this event such an important one.

Meanwhile, Dexter Johnson’s (Nanoclast blog in the IEEE website) July 21, 2011 posting poses a question,

While the nanocomposite scaffold is a critical element to the artificial organ, perhaps no less important was the bioreactor used to grow the stem cells onto it, which was developed at Harvard Bioscience.

If you needed any evidence of how nanotechnology is not only interdisciplinary, but also international, you could just cite this case: UK-developed nanocomposite for the scaffolding material, US-based bioreactor in which the stem cells were grown onto the scaffolding and a Swedish-based medical institute to perform the transplant.

So I ask, which country or region is going to get rich from the breakthrough?

It’s an interesting question and I don’t think I would have framed it in quite that fashion largely because I don’t tend to think of countries or regions getting wealthy from biomedical products since pharmaceutical companies tend to be internationally based. Is Switzerland richer for Novartis?

I suppose I’m a product of the Canadian landscape from which I spring so I think of trees and mines as making a country or region richer as they are inextricably linked to their environment but pharmaceuticals or biomedical appliances can be manufactured anywhere. Consequently, a synthetic organ could be manufactured anywhere once the technology becomes easily available. Who gets rich from this development? I suspect that will be a person or persons if anyone but, not a region or a country.

Getting back to Beyene, here are more details from the July 7, 2011 BBC News article by Michelle Roberts,

Dr Alex Seifalian and his team used this fragile structure [the scaffold] to create a replacement for the patient, whose own windpipe was ravaged by an inoperable tumour.

Despite aggressive chemotherapy and radiotherapy, the cancer had grown to the size of a golf ball and was blocking his breathing. Without a transplant he would have died.

During a 12-hour operation Professor Macchiarini removed all of the tumour and the diseased windpipe and replaced it with the tailor-made replica [now covered with tissue grown from the patient’s bone marrow tricked into growing like cells found in a trachea].

…

And, importantly, Mr Beyene’s body will accept it as its own, meaning he will not need to take the strong anti-rejection drugs that other transplant patients have to.

Professor Macchiarini said this was the real breakthrough.

“Thanks to nanotechnology, this new branch of regenerative medicine, we are now able to produce a custom-made windpipe within two days or one week.

“This is a synthetic windpipe. The beauty of this is you can have it immediately. There is no delay. This technique does not rely on a human donation.”

He said many other organs could be repaired or replaced in the same way.

A month on from his operation, Mr Beyene is still looking weak, but well.

Sitting up in his hospital bed, he said: “I was very scared, very scared about the operation. But it was live or die.”

My best wishes to Beyene and his family who are also pioneers.

 

The memristor rises; commercialization and academic research in the US; carbon nanotubes could be made safer than we thought

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In 2008, two memristor papers were published in Nature and Nature Nanotechnology, respectively. In the first (Nature, May 2008 [article still behind a paywall], a team at HP Labs claimed they had proved the existence of memristors (a fourth member of electrical engineering’s ‘Holy Trinity of the capacitor, resistor, and inductor’). In the second paper (Nature Nanotechnology, July 2008 [article still behind a paywall]) the team reported that they had achieved engineering control.

I mention this because (a) there’s some new excitement about memristors and (b) I love the story (you can read my summary of the 2008 story here on the Nanotech Mysteries wiki).

Unbeknownst to me in 2008, there was another team, located in Japan, whose work  on slime mould inspired research by a group at the University of California San Diego (UC San Diego)  which confirmed theorist Leon Chua’s (he first suggested memristors existed in 1971) intuition that biological organisms used memristive systems to learn. From an article (Synapse on a Chip) by Surf daddy Orca on the HPlus magazine site,

Experiments with slime molds in 2008 by Tetsu Saisuga at Hokkaido University in Sapporo sparked additional research at the University of California, San Diego by Max Di Ventra. Di Ventra was familiar with Chua’s work and built a memristive circuit that was able to learn and predict future signals. This ability turns out to be similar to the electrical activity involved in the ebb and flow of potassium and sodium ions across cellular membranes: synapses altering their response according to the frequency and strength of signals. New Scientist reports that Di Ventra’s work confirmed Chua’s suspicions that “synapses were memristors.” “The ion channel was the missing circuit element I was looking for,” says Chua, “and it already existed in nature.”

Fast forward to 2010 and a team at the University of Michigan led by Dr. Wei Lu showing how synapses behave like memristors (published in Nano Letters, DOI: 10.1021/nl904092h [article behind paywall]). (Fromthe  HPlus site article)

Scientific American describes a US military-funded project that is trying to use the memristor “to make neural computing a reality.” DARPA’s Systems of Neuromorphic Adaptive Plastic Scalable Electronics Program (SyNAPSE) is funded to create “electronic neuromorphic machine technology that is scalable to biological levels.”

I’m not sure if the research in Michigan and elsewhere is being funded by DARPA (the US Dept. of Defense’s Defense Advanced Research Project Agency) although it seems likely.

In the short term, scientists talk about energy savings (no need to reboot your computer when you turn it back on). In the longer term, they talk about hardware being able to learn. (Thanks to the Foresight Institute for the latest update on the memristor story and the pointer to HPlus.) Do visit the HPlus site as there are some videos of scientists talking about memristors and additional information (there’s yet another team working on research that is tangentially related).

Commercializing academic research in US

Thanks to Dave Bruggeman at the Pasco Phronesis blog who’s posted some information about a White House Request for Information (RFI) on commercializing academic research. This is of particular interest not just because of the discussion about innovation in Canada but also because the US National Nanotechnology Initiative’s report to PCAST (President’s Council of Advisors on Science and Technology, my comments about the webcast of the proceedings here). From the Pasco Phronesis posting about the NNI report,

While the report notes that the U.S. continues to have a strong nanotechnology sector and corresponding support from the government. However, as with most other economic and research sectors, the rest of the world is catching up, or spending enough to try and catch up to the United States.

According to the report, more attention needs to be paid to commercialization efforts (a concern not unique to nanotechnology).

I don’t know how long the White House’s RFI has been under development but it was made public at the end of March 2010 just weeks after the latest series of reports to PCAST. As for the RFI itself, from the Pasco Phronesis posting about it,

The RFI questions are organized around two basic concerns:

  • Seeking ideas for supporting the commercialization and diffusion of university research. This would include best practices, useful models, metrics (with evidence of their success), and suggested changes in federal policy and/or research funding. In addition, the RFI is interested in how commercialization ecosystems can be developed where none exist.
  • Collecting data on private proof of concept centers (POCCs). These entities seek to help get research over the so-called “Valley of Death” between demonstrable research idea and final commercial product. The RFI is looking for similar kinds of information as for commercialization in general: best practices, metrics, underlying conditions that facilitate such centers.

I find the news of this RFI a little surprising since I had the impression that commercialization of academic research in the US is far more advanced than it is here in Canada. Mind you, that impression is based on a conversation I had with a researcher a year ago who commented that his mentor at a US university rolled out more than 1 start up company every year. As I understand it researchers in Canada may start up one or two companies in their career but never a series of them.

Carbon nanotubes, is exposure ok?

There’s some new research which suggests that carbon nanotubes can be broken down by an enzyme. From the news item on Nanowerk,

A team of Swedish and American scientists has shown for the first time that carbon nanotubes can be broken down by an enzyme – myeloperoxidase (MPO) – found in white blood cells. Their discoveries are presented in Nature Nanotechnology (“Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation”) and contradict what was previously believed, that carbon nanotubes are not broken down in the body or in nature. The scientists hope that this new understanding of how MPO converts carbon nanotubes into water and carbon dioxide can be of significance to medicine.

“Previous studies have shown that carbon nanotubes could be used for introducing drugs or other substances into human cells,” says Bengt Fadeel, associate professor at the Swedish medical university Karolinska Institutet. “The problem has been not knowing how to control the breakdown of the nanotubes, which can caused unwanted toxicity and tissue damage. Our study now shows how they can be broken down biologically into harmless components.”

I believe they tested single-walled carbon nanotubes (CNTs) only as the person who wrote the news release seems unaware that mutil-walled CNTs also exist. In any event, this could be very exciting if this research holds up under more testing.