Harvard University researchers, in collaboration with colleagues from Emory University, have developed the first fully autonomous biohybrid fish from human stem-cell derived cardiac muscle cells. The artificial fish swims by recreating the muscle contractions of a pumping heart, bringing researchers one step closer to developing a more complex artificial muscular pump and providing a platform to study heart disease like arrhythmia.
“Our ultimate goal is to build an artificial heart to replace a malformed heart in a child,” said Kit Parker, the Tarr Family Professor of Bioengineering and Applied Physics at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and senior author of the paper. “Most of the work in building heart tissue or hearts, including some work we have done, is focused on replicating the anatomical features or replicating the simple beating of the heart in the engineered tissues. But here, we are drawing design inspiration from the biophysics of the heart, which is harder to do. Now, rather than using heart imaging as a blueprint, we are identifying the key biophysical principles that make the heart work, using them as design criteria, and replicating them in a system, a living, swimming fish, where it is much easier to see if we are successful.”
The research is published in Science.
The biohybrid fish developed by the team builds off previous research from Parker’s Disease Biophysics Group. In 2012, the lab used cardiac muscle cells from rats to build a jellyfish-like biohybrid pump and in 2016 the researchers developed a swimming, artificial stingray also from rat heart muscle cells.
In this research, the team built the first autonomous biohybrid device made from human stem-cell derived cardiomyocytes. This device was inspired by the shape and swimming motion of a zebrafish. Unlike previous devices, the biohybrid zebrafish has two layers of muscle cells, one on each side of the tail fin. When one side contracts, the other stretches. That stretch triggers the opening of a mechanosensitive protein channel, which causes a contraction, which triggers a stretch and so on and so forth, leading to a closed loop system that can propel the fish for more than 100 days.
“By leveraging cardiac mechano-electrical signaling between two layers of muscle, we recreated the cycle where each contraction results automatically as a response to the stretching on the opposite side,” said Keel Yong Lee, a postdoctoral fellow at SEAS and co-first author of the study. “The results highlight the role of feedback mechanisms in muscular pumps such as the heart.”
The researchers also engineered an autonomous pacing node, like a pacemaker, which controls the frequency and rhythm of these spontaneous contractions. Together, the two layers of muscle and the autonomous pacing node enabled the generation of continuous, spontaneous, and coordinated, back-and-forth fin movements.
“Because of the two internal pacing mechanisms, our fish can live longer, move faster and swim more efficiently than previous work,” said Sung-Jin Park, a former postdoctoral fellow in the Disease Biophysics Group at SEAS and co-first author of the study. “This new research provides a model to investigate mechano-electrical signaling as a therapeutic target of heart rhythm management and for understanding pathophysiology in sinoatrial node dysfunctions and cardiac arrhythmia.”
Park is currently an Assistant Professor at the Coulter Department of Biomedical Engineering at Georgia Institute of Technology and Emory University School of Medicine.
Unlike a fish in your refrigerator, this biohybrid fish improves with age. Its muscle contraction amplitude, maximum swimming speed, and muscle coordination all increased for the first month as the cardiomyocyte cells matured. Eventually, the biohybrid fish reached speeds and swimming efficacy similar to zebrafish in the wild.
Next, the team aims to build even more complex biohybrid devices from human heart cells.
“I could build a model heart out of Play-Doh, it doesn’t mean I can build a heart,” said Parker. “You can grow some random tumor cells in a dish until they curdle into a throbbing lump and call it a cardiac organoid. Neither of those efforts is going to, by design, recapitulate the physics of a system that beats over a billion times during your lifetime while simultaneously rebuilding its cells on the fly. That is the challenge. That is where we go to work.”
The research was co-authored by David G. Matthews, Sean L. Kim, Carlos Antonio Marquez, John F. Zimmerman, Herdeline Ann M. Ardona, Andre G. Kleber and George V. Lauder.
It was supported in part by National Institutes of Health National Center for Advancing Translational Sciences grant UH3TR000522, and National Science Foundation Materials Research Science and Engineering Center grant DMR-142057.
An autonomously swimming biohybrid fish, designed with a focus on two key regulatory features of the human heart, has revealed the importance of feedback mechanisms in muscular pumps (such as the heart). The findings could one day help inform the development of an artificial heart made from living muscle cells. Biohybrid systems – devices containing both biological and artificial components – are an effective way to investigate the physiological control mechanisms in biological organisms and to discover bio-inspired robotic solutions to a host of pressing concerns, including those related to human health. When it comes to natural fluid transport pumps, like those that circulate blood, the performance of biohybrid systems has been lacking, however. Here, researchers considered whether two functional regulatory features of the heart — mechanoelectrical signaling and automaticity — could be transferred to a synthetic analog of another fluid transport system: a swimming fish. Lee et al. developed an autonomously swimming fish constructed from a bilayer of human cardiac cells; the muscular bilayer was integrated using tissue engineering techniques. Lee and team were able to control muscle contractions in the biohybrid fish using external optogenetic stimulation, allowing the fish analog to swim. In tests, the biohybrid fish outperformed the locomotory speed of previous biohybrid muscular systems, the authors say. It maintained spontaneous activity for 108 days. By contrast, say the authors, biohybrid fish equipped with single-layered muscle showed deteriorating activity within the first month. The data in this study demonstrate the potential of muscular bilayer systems and mechanoelectrical signaling as a means to promote maturation of in vitro muscle tissues, write Lee and colleagues. “Taken together,” the authors conclude, “the technology described here may represent foundational work toward the goal of creating autonomous systems capable of homeostatic regulation and adaptive behavioral control.”
For reporters interested in trends, this work builds upon previous work published in a July 2016 study in Science, in which Sung-jin Park et al. used cardiac cells from rats to develop a self-propelling ray fish analog.
This story got me to thinking about what happens when any kind of implant company (pacemaker, deep brain stimulator, etc.) goes bankrupt or is acquired by another company with a different business model.
As I worked on this piece, more issues were raised and the scope expanded to include prosthetics along with implants while the focus narrowed to neuro as in, neural implants and neuroprosthetics. At the same time, I found salient examples for this posting in other medical advances such as gene editing.
In sum, all references to implants and prosthetics are to neural devices and some issues are illustrated with salient examples from other medical advances (specifically, gene editing).
Medical implants are devices or tissues that are placed inside or on the surface of the body. Many implants are prosthetics, intended to replace missing body parts. Other implants deliver medication, monitor body functions, or provide support to organs and tissues.
As for what constitutes a neural implant/neuroprosthetic, there’s this from Emily Waltz’s January 20, 2020 article (How Do Neural Implants Work? Neural implants are used for deep brain stimulation, vagus nerve stimulation, and mind-controlled prostheses) for the Institute of Electrical and Electronics Engineers (IEEE) Spectrum magazine,
A neural implant, then, is a device—typically an electrode of some kind—that’s inserted into the body, comes into contact with tissues that contain neurons, and interacts with those neurons in some way.
Now, let’s start with the recent near bankruptcy of a retinal implant company.
Barbara Campbell was walking through a New York City subway station during rush hour when her world abruptly went dark. For four years, Campbell had been using a high-tech implant in her left eye that gave her a crude kind of bionic vision, partially compensating for the genetic disease that had rendered her completely blind in her 30s. “I remember exactly where I was: I was switching from the 6 train to the F train,” Campbell tells IEEE Spectrum. “I was about to go down the stairs, and all of a sudden I heard a little ‘beep, beep, beep’ sound.’”
It wasn’t her phone battery running out. It was her Argus II retinal implant system powering down. The patches of light and dark that she’d been able to see with the implant’s help vanished.
Terry Byland is the only person to have received this kind of implant in both eyes. He got the first-generation Argus I implant, made by the company Second Sight Medical Products, in his right eye in 2004, and the subsequent Argus II implant in his left 11 years later. He helped the company test the technology, spoke to the press movingly about his experiences, and even met Stevie Wonder at a conference. “[I] went from being just a person that was doing the testing to being a spokesman,” he remembers.
Yet in 2020, Byland had to find out secondhand that the company had abandoned the technology and was on the verge of going bankrupt. While his two-implant system is still working, he doesn’t know how long that will be the case. “As long as nothing goes wrong, I’m fine,” he says. “But if something does go wrong with it, well, I’m screwed. Because there’s no way of getting it fixed.”
Ross Doerr, another Second Sight patient, doesn’t mince words: “It is fantastic technology and a lousy company,” he says. He received an implant in one eye in 2019 and remembers seeing the shining lights of Christmas trees that holiday season. He was thrilled to learn in early 2020 that he was eligible for software upgrades that could further improve his vision. Yet in the early months of the COVID-19 pandemic, he heard troubling rumors about the company and called his Second Sight vision-rehab therapist. “She said, ‘Well, funny you should call. We all just got laid off,’ ” he remembers. “She said, ‘By the way, you’re not getting your upgrades.’ ”
These three patients, and more than 350 other blind people around the world with Second Sight’s implants in their eyes, find themselves in a world in which the technology that transformed their lives is just another obsolete gadget. One technical hiccup, one broken wire, and they lose their artificial vision, possibly forever. To add injury to insult: A defunct Argus system in the eye could cause medical complications or interfere with procedures such as MRI scans, and it could be painful or expensive to remove.
After Second Sight discontinued its retinal implant in 2019 and nearly went out of business in 2020, a public offering in June 2021 raised US $57.5 million at $5 per share. The company promised to focus on its ongoing clinical trial of a brain implant, called Orion, that also provides artificial vision. But its stock price plunged to around $1.50, and in February 2022, just before this article was published, the company announced a proposed merger with an early-stage biopharmaceutical company called Nano Precision Medical (NPM). None of Second Sight’s executives will be on the leadership team of the new company, which will focus on developing NPM’s novel implant for drug delivery.The company’s current leadership declined to be interviewed for this article but did provide an emailed statement prior to the merger announcement. It said, in part: “We are a recognized global leader in neuromodulation devices for blindness and are committed to developing new technologies to treat the broadest population of sight-impaired individuals.”
It’s unclear what Second Sight’s proposed merger means for Argus patients. The day after the merger was announced, Adam Mendelsohn, CEO of Nano Precision Medical, told Spectrum that he doesn’t yet know what contractual obligations the combined company will have to Argus and Orion patients. But, he says, NPM will try to do what’s “right from an ethical perspective.” The past, he added in an email, is “simply not relevant to the new future.”
Second Sight may have given up on its retinal implant, but other companies still see a need—and a market—for bionic vision without brain surgery. Paris-based Pixium Vision is conducting European and U.S. feasibility trials to see if its Prima system can help patients with age-related macular degeneration, a much more common condition than retinitis pigmentosa.
Daniel Palanker, a professor of ophthalmology at Stanford University who licensed his technology to Pixium, says the Prima implant is smaller, simpler, and cheaper than the Argus II. But he argues that Prima’s superior image resolution has the potential to make Pixium Vision a success. “If you provide excellent vision, there will be lots of patients,” he tells Spectrum. “If you provide crappy vision, there will be very few.”
Some clinicians involved in the Argus II work are trying to salvage what they can from the technology. Gislin Dagnelie, an associate professor of ophthalmology at Johns Hopkins University School of Medicine, has set up a network of clinicians who are still working with Argus II patients. The researchers are experimenting with a thermal camera to help users see faces, a stereo camera to filter out the background, and AI-powered object recognition. These upgrades are unlikely to result in commercial hardware today but could help future vision prostheses.
Failure is an inevitable part of innovation. The Argus II was an innovative technology, and progress made by Second Sight may pave the way for other companies that are developing bionic vision systems. But for people considering such an implant in the future, the cautionary tale of Argus patients left in the lurch may make a tough decision even tougher. Should they take a chance on a novel technology? If they do get an implant and find that it helps them navigate the world, should they allow themselves to depend upon it?
Abandoning the Argus II technology—and the people who use it—might have made short-term financial sense for Second Sight, but it’s a decision that could come back to bite the merged company if it does decide to commercialize a brain implant, believes Doerr.
For anyone curious about retinal implant technology (specifically the Argus II), I have a description in a June 30, 2015 posting.
Speculations and hopes for neuroprosthetics
The field of neuroprosthetics is very active. Dr Arthur Saniotis and Prof Maciej Henneberg have written an article where they speculate about the possibilities of a neuroprosthetic that may one day merge with neurons in a February 21, 2022 Nanowerk Spotlight article,
For over a generation several types of medical neuroprosthetics have been developed, which have improved the lives of thousands of individuals. For instance, cochlear implants have restored functional hearing in individuals with severe hearing impairment.
Further advances in motor neuroprosthetics are attempting to restore motor functions in tetraplegic, limb loss and brain stem stroke paralysis subjects.
Currently, scientists are working on various kinds of brain/machine interfaces [BMI] in order to restore movement and partial sensory function. One such device is the ‘Ipsihand’ that enables movement of a paralyzed hand. The device works by detecting the recipient’s intention in the form of electrical signals, thereby triggering hand movement.
Another recent development is the 12 month BMI gait neurohabilitation program that uses a visual-tactile feedback system in combination with a physical exoskeleton and EEG operated AI actuators while walking. This program has been tried on eight patients with reported improvements in lower limb movement and somatic sensation.
Surgically placed electrode implants have also reduced tremor symptoms in individuals with Parkinson’s disease.
Although neuroprosthetics have provided various benefits they do have their problems. Firstly, electrode implants to the brain are prone to degradation, necessitating new implants after a few years. Secondly, as in any kind of surgery, implanted electrodes can cause post-operative infection and glial scarring. Furthermore, one study showed that the neurobiological efficacy of an implant is dependent on the rate of speed of its insertion.
But what if humans designed a neuroprosthetic, which could bypass the medical glitches of invasive neuroprosthetics? However, instead of connecting devices to neural networks, this neuroprosthetic would directly merge with neurons – a novel step. Such a neuroprosthetic could radically optimize treatments for neurodegenerative disorders and brain injuries, and possibly cognitive enhancement [emphasis mine].
An interesting feature of their nanobot neuroprosthetic is that it has been inspired from nature by way of endomyccorhizae – a type of plant/fungus symbiosis, which is over four hundred million years old. During endomyccorhizae, fungi use numerous threadlike projections called mycelium that penetrate plant roots, forming colossal underground networks with nearby root systems. During this process fungi take up vital nutrients while protecting plant roots from infections – a win-win relationship. Consequently, the nano-neuroprosthetic has been named ‘endomyccorhizae ligand interface’, or ‘ELI’ for short.
The Spotlight article goes on to describe how these nanobots might function. As for the possibility of cognitive enhancement, I wonder if that might come to be described as a form of ‘artificial intelligence’.
(Dr Arthur Saniotis and Prof Maciej Henneberg are both from the Department of Anthropology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences; and Biological Anthropology and Comparative Anatomy Research Unit, Adelaide Medical School, University of Adelaide. Abdul-Rahman Sawalma who’s listed as an author on the 2018 paper is from the Palestinian Neuroscience Initiative, Al-Quds University, Beit Hanina, Palestine.)
Saniotis and Henneberg’s Spotlight article presents an optimistic view of neuroprosthetics. It seems telling that they cite cochlear implants as a success story when it is viewed by many as ethically fraught (see the Cochlear implant Wikipedia entry; scroll down to ‘Criticism and controversy’).
Technologist: What are the potential consequences of accepting the “augmented human” in society?
Gregor Wolbring: There are many that we might not even envision now. But let me focus on failure and obsolescence [emphasis mine], two issues that are rarely discussed. What happens when the mechanisms fails in the middle of an action? Failure has hazardous consequences, but obsolescence has psychological ones. …. The constant surgical intervention needed to update the hardware may not be feasible. A person might feel obsolete if she cohabits with others using a newer version.
T. Are researchers working on prosthetics sometimes disconnected from reality?
G. W. Students engaged in the development of prosthetics have to learn how to think in societal terms and develop a broader perspective. Our education system provides them with a fascination for clever solutions to technological challenges but not with tools aiming at understanding the consequences, such as whether their product might increase or decrease social justice.
Wolbring is a professor at the University of Calgary’s Cumming School of Medicine (profile page) who writes on social issues to do with human enhancement/ augmentation. As well,
Some of his areas of engagement are: ability studies including governance of ability expectations, disability studies, governance of emerging and existing sciences and technologies (e.g. nanoscale science and technology, molecular manufacturing, aging, longevity and immortality, cognitive sciences, neuromorphic engineering, genetics, synthetic biology, robotics, artificial intelligence, automatization, brain machine interfaces, sensors), impact of science and technology on marginalized populations, especially people with disabilities he governance of bodily enhancement, sustainability issues, EcoHealth, resilience, ethics issues, health policy issues, human rights and sport.
I’d classify Second Sight as a tech startup company and they have a high rate of failure, which may not have been clear to the patients who had the implants. Clinical trials can present problems too as this excerpt from my September 17, 2020 posting notes,
“In 2003, neurologist Helen Mayberg of Emory University in Atlanta began to test a bold, experimental treatment for people with severe depression, which involved implanting metal electrodes deep in the brain in a region called area 25 [emphases mine]. The initial data were promising; eventually, they convinced a device company, St. Jude Medical in Saint Paul, to sponsor a 200-person clinical trial dubbed BROADEN.
This month [October 2017], however, Lancet Psychiatry reported the first published data on the trial’s failure. The study stopped recruiting participants in 2012, after a 6-month study in 90 people failed to show statistically significant improvements between those receiving active stimulation and a control group, in which the device was implanted but switched off.
… a tricky dilemma for companies and research teams involved in deep brain stimulation (DBS) research: If trial participants want to keep their implants [emphases mine], who will take responsibility—and pay—for their ongoing care? And participants in last week’s meeting said it underscores the need for the growing corps of DBS researchers to think long-term about their planned studies.”
“It becomes part of you,” Patient 6 said, describing the technology that enabled her, after 45 years of severe epilepsy, to halt her disabling seizures. Electrodes had been implanted on the surface of her brain that would send a signal to a hand-held device when they detected signs of impending epileptic activity. On hearing a warning from the device, Patient 6 knew to take a dose of medication to halt the coming seizure.
“You grow gradually into it and get used to it, so it then becomes a part of every day,” she told Frederic Gilbert, an ethicist who studies brain–computer interfaces (BCIs) at the University of Tasmania in Hobart, Australia. “It became me,” she said. [emphasis mine]
Symbiosis is a term, borrowed from ecology, that means an intimate co-existence of two species for mutual advantage. As technologists work towards directly connecting the human brain to computers, it is increasingly being used to describe humans’ potential relationship with artificial intelligence. [emphasis mine]
For a lot of people these devices are or could be life-changing. At the same time, there are a number of different issues related to implants/prosthetics; the following is not an exhaustive list. As Wolbring notes, issues that we can’t begin to imagine now are likely to emerge as these medical advances become more ubiquitous.
Assistive technologies are almost always portrayed as helpful. For example, a cochlear implant gives people without hearing the ability to hear. The assumption is that this is always a good thing—unless you’re a deaf person who wants to define the problem a little differently. Who gets to decide what is good and ‘normal’ and what is desirable?
While the cochlear implant is the most extreme example I can think of, there are variations of these questions throughout the ‘disability’ communities.
Also, as Wolbring notes in his interview with the Technologist.eu, the education system tends to favour technological solutions which don’t take social issues into account. Wolbring cites social justice issues when he mentions failure and obsolescence.
Technical failures and obsolescence
The story, excerpted earlier in this posting, opened with a striking example of a technical failure at an awkward moment; a blind woman depending on her retinal implant loses all sight as she maneuvers through a subway station in New York City.
Aside from being an awful way to find out the company supplying and supporting your implant is in serious financial trouble and can’t offer assistance or repair, the failure offers a preview of what could happen as implants and prosthetics become more commonly used.
Keeping up/fomo (fear of missing out)/obsolescence
It used to be called ‘keeping up with the Joneses, it’s the practice of comparing yourself and your worldly goods to someone else(‘s) and then trying to equal what they have or do better. Usually, people want to have more and better than the mythical Joneses.
These days, the phenomenon (which has been expanded to include social networking) is better known as ‘fomo’ or fear of missing out (see the Fear of missing out Wikipedia entry).
Whatever you want to call it, humanity’s competitive nature can be seen where technology is concerned. When I worked in technology companies, I noticed that hardware and software were sometimes purchased for features that were effectively useless to us. But, not upgrading to a newer version was unthinkable.
Call it fomo or ‘keeping up with the Joneses’, it’s a powerful force and when people (and even companies) miss out or can’t keep up, it can lead to a sense of inferiority in the same way that having an obsolete implant or prosthetic could.
Could there be a neural implant/neuroprosthetic divide? There is already a digital divide (from its Wikipedia entry),
The digital divide is a gap between those who have access to new technology and those who do not … people without access to the Internet and other ICTs [information and communication technologies] are at a socio-economic disadvantage because they are unable or less able to find and apply for jobs, shop and sell online, participate democratically, or research and learn.
After reading Wolbring’s comments, it’s not hard to imagine a neural implant/neuroprosthetic divide with its attendant psychological and social consequences.
What kind of human am I?
There are other issues as noted in my September 17, 2020 posting. I’ve already mentioned ‘patient 6’, the woman who developed a symbiotic relationship with her brain/computer interface. This is how the relationship ended,
… He [Frederic Gilbert, ethicist] is now preparing a follow-up report on Patient 6. The company that implanted the device in her brain to help free her from seizures went bankrupt. The device had to be removed.
… Patient 6 cried as she told Gilbert about losing the device. … “I lost myself,” she said.
“It was more than a device,” Gilbert says. “The company owned the existence of this new person.”
More recently, Hugh Herr, an Associate Professor at the Massachusetts Institute of Technology (MIT), leader of the Biomechatronics research group at MIT’s Media Lab, a double amputee, and prosthetic enthusiast, starred in the recent (February 23, 2022) broadcast of ‘Augmented‘ on the Public Broadcasting Service (PBS) science programme, Nova.
I found ‘Augmented’ a little offputting as it gave every indication of being an advertisement for Herr’s work in the form of a hero’s journey. I was not able to watch more than 10 mins. This preview gives you a pretty good idea of what it was like although the part in ‘Augmented, where he says he’d like to be a cyborg hasn’t been included,
At a guess, there were a few talking heads (taking up from 10%-20% of the running time) who provided some cautionary words to counterbalance the enthusiasm in the rest of the programme. It’s a standard approach designed to give the impression that both sides of a question are being recognized. The cautionary material is usually inserted past the 1/2 way mark while leaving several minutes at the end for returning to the more optimistic material.
Written by Paul Hochman for Fast Company, Bionic Legs, iLimbs, and Other Super-Human Prostheses [ETA March 23, 2022: an updated version of the article is now on Genius.com] delves further into the world where people may be willing to trade a healthy limb for a prosthetic. From the article,
There are many advantages to having your leg amputated.
Pedicure costs drop 50% overnight. A pair of socks lasts twice as long. But Hugh Herr, the director of the Biomechatronics Group at the MIT Media Lab, goes a step further. “It’s actually unfair,” Herr says about amputees’ advantages over the able-bodied. “As tech advancements in prosthetics come along, amputees can exploit those improvements. They can get upgrades. A person with a natural body can’t.”
Herr is not the only one who favours prosthetics (also from the Hochman article),
This influx of R&D cash, combined with breakthroughs in materials science and processor speed, has had a striking visual and social result: an emblem of hurt and loss has become a paradigm of the sleek, modern, and powerful. Which is why Michael Bailey, a 24-year-old student in Duluth, Georgia, is looking forward to the day when he can amputate the last two fingers on his left hand.
“I don’t think I would have said this if it had never happened,” says Bailey, referring to the accident that tore off his pinkie, ring, and middle fingers. “But I told Touch Bionics I’d cut the rest of my hand off if I could make all five of my fingers robotic.”
But Bailey is most surprised by his own reaction. “When I’m wearing it, I do feel different: I feel stronger. As weird as that sounds, having a piece of machinery incorporated into your body, as a part of you, well, it makes you feel above human.[emphasis mine] It’s a very powerful thing.”
My September 17, 2020 posting touches on more ethical and social issues including some of those surrounding consumer neurotechnologies or brain-computer interfaces (BCI). Unfortunately, I don’t have space for these issues here.
In the IEEE Spectrum article, a tech start-up company, Second Sight, ran into financial trouble and is acquired by a company that has no plans to develop Second Sight’s core technology. The people implanted with the Argus II technology have been stranded as were ‘patient 6’ and others participating in the clinical trial described in the July 24, 2019 article by Liam Drew for Nature Outlook: The brain mentioned earlier in this posting.
I don’t know anything about the business bankruptcy mentioned in the Drew article but one of the business problems described in the IEEE Spectrum article suggests that Second Sight was founded before answering a basic question, “What is the market size for this product?”
On 18 July 2019, Second Sight sent Argus patients a letter saying it would be phasing out the retinal implant technology to clear the way for the development of its next-generation brain implant for blindness, Orion, which had begun a clinical trial with six patients the previous year. …
“The leadership at the time didn’t believe they could make [the Argus retinal implant] part of the business profitable,” Greenberg [Robert Greenberg, Second Sight co-founder] says. “I understood the decision, because I think the size of the market turned out to be smaller than we had thought.”
The question of whether a medical procedure or medicine can be profitable (or should the question be sufficiently profitable?) was referenced in my April 26, 2019 posting in the context of gene editing and personalized medicine
Edward Abrahams, president of the Personalized Medicine Coalition (US-based), advocates for personalized medicine while noting in passing, market forces as represented by Goldman Sachs in his May 23, 2018 piece for statnews.com (Note: A link has been removed),
Goldman Sachs, for example, issued a report titled “The Genome Revolution.” It argues that while “genome medicine” offers “tremendous value for patients and society,” curing patients may not be “a sustainable business model.” [emphasis mine] The analysis underlines that the health system is not set up to reap the benefits of new scientific discoveries and technologies. Just as we are on the precipice of an era in which gene therapies, gene-editing, and immunotherapies promise to address the root causes of disease, Goldman Sachs says that these therapies have a “very different outlook with regard to recurring revenue versus chronic therapies.”
The ‘Glybera’ story in my July 4, 2019 posting (scroll down about 40% of the way) highlights the issue with “recurring revenue versus chronic therapies,”
It cost $1M for a single treatment and that single treatment is good for at least 10 years.
Pharmaceutical companies make their money from repeated use of their medicaments and Glybera required only one treatment so the company priced it according to how much they would have gotten for repeated use, $100,000 per year over a 10 year period. The company was not able to persuade governments and/or individuals to pay the cost
In the end, 31 people got the treatment, most of them received it for free through clinical trials.
For rich people only?
Megan Devlin’s March 8, 2022 article for the Daily Hive announces a major research investment into medical research (Note: A link has been removed),
Vancouver [Canada] billionaire Chip Wilson revealed Tuesday [March 8, 2022] that he has a rare genetic condition that causes his muscles to waste away, and announced he’s spending $100 million on research to find a cure.
His condition is called facio-scapulo-humeral muscular dystrophy, or FSHD for short. It progresses rapidly in some people and more slowly in others, but is characterized by progressive muscle weakness starting the the face, the neck, shoulders, and later the lower body.
“I’m out for survival of my own life,” Wilson said.
“I also have the resources to do something about this which affects so many people in the world.”
Wilson hopes the $100 million will produce a cure or muscle-regenerating treatment by 2027.
“This could be one of the biggest discoveries of all time, for humankind,” Wilson said. “Most people lose muscle, they fall, and they die. If we can keep muscle as we age this can be a longevity drug like we’ve never seen before.”
According to rarediseases.org, FSHD affects between four and 10 people out of every 100,000 [emphasis mine], Right now, therapies are limited to exercise and pain management. There is no way to stall or reverse the disease’s course.
Wilson is best known for founding athleisure clothing company Lululemon. He also owns the most expensive home in British Columbia, a $73 million mansion in Vancouver’s Kitsilano neighbourhood.
Let’s see what the numbers add up to,
4 – 10 people out of 100,000
40 – 100 people out of 1M
1200 – 3,000 people out of 30M (let’s say this is Canada’s population)\
12,000 – 30,000 people out of 300M (let’s say this is the US’s population)
42,000 – 105,000 out of 1.115B (let’s say this is China’s population)
The rough total comes to 55,200 to 138,000 people between three countries with a combined population total of 1.445B. Given how business currently operates, it seems unlikely that any company will want to offer Wilson’s hoped for medical therapy although he and possibly others may benefit from a clinical trial.
Should profit or wealth be considerations?
The stories about the patients with the implants and the patients who need Glybera are heartbreaking and point to a question not often asked when medical therapies and medications are developed. Is the profit model the best choice and, if so, how much profit?
I have no answer to that question but I wish it was asked by medical researchers and policy makers.
As for wealthy people dictating the direction for medical research, I don’t have answers there either. I hope the research will yield applications and/or valuable information for more than Wilson’s disease.
It’s his money after all
Wilson calls his new venture, SolveFSHD. It doesn’t seem to be affiliated with any university or biomedical science organization and it’s not clear how the money will be awarded (no programmes, no application procedure, no panel of experts). There are three people on the team, Eva R. Chin, scientist and executive director, Chip Wilson, SolveFSHD founder/funder, and FSHD patient, and Neil Camarta, engineer, executive (fossil fuels and clean energy), and FSHD patient. There’s also a Twitter feed (presumably for the latest updates): https://twitter.com/SOLVEFSHD.
Low Tide Properties, the real estate arm of Lululemon founder Chip Wilson [emphasis mine], has submitted a new development permit application to build a 148-ft-tall, eight-storey, mixed-use commercial building in the False Creek Flats of Vancouver.
The proposal, designed by local architectural firm Musson Cattell Mackey Partnership, calls for 236,000 sq ft of total floor area, including 105,000 sq ft of general office space, 102,000 sq ft of laboratory space [emphasis mine], and 5,000 sq ft of ground-level retail space. An outdoor amenity space for building workers will be provided on the rooftop.
[next door] The 2001-built, five-storey building at 1618 Station Street immediately to the west of the development site is also owned by Low Tide Properties [emphasis mine]. The Ferguson, the name of the existing building, contains about 79,000 sq ft of total floor area, including 47,000 sq ft of laboratory space and 32,000 sq ft of general office space. Biotechnology company Stemcell technologies [STEMCELL] Technologies] is the anchor tenant [emphasis mine].
I wonder if this proposed new building will house SolveFSHD and perhaps other FSHD-focused enterprises. The proximity of STEMCELL Technologies could be quite convenient. In any event, $100M will buy a lot (pun intended).
Issues I’ve described here in the context of neural implants/neuroprosthetics and cutting edge medical advances are standard problems not specific to these technologies/treatments:
What happens when the technology fails (hopefully not at a critical moment)?
What happens when your supplier goes out of business or discontinues the products you purchase from them?
How much does it cost?
Who can afford the treatment/product? Will it only be for rich people?
Will this technology/procedure/etc. exacerbate or create new social tensions between social classes, cultural groups, religious groups, races, etc.?
Of course, having your neural implant fail suddenly in the middle of a New York City subway station seems a substantively different experience than having your car break down on the road.
There are, of course, there are the issues we can’t yet envision (as Wolbring notes) and there are issues such as symbiotic relationships with our implants and/or feeling that you are “above human.” Whether symbiosis and ‘implant/prosthetic superiority’ will affect more than a small number of people or become major issues is still to be determined.
There’s a lot to be optimistic about where new medical research and advances are concerned but I would like to see more thoughtful coverage in the media (e.g., news programmes and documentaries like ‘Augmented’) and more thoughtful comments from medical researchers.
Of course, the biggest issue I’ve raised here is about the current business models for health care products where profit is valued over people’s health and well-being. it’s a big question and I don’t see any definitive answers but the question put me in mind of this quote (from a September 22, 2020 obituary for US Supreme Court Justice Ruth Bader Ginsburg by Irene Monroe for Curve),
Ginsburg’s advocacy for justice was unwavering and showed it, especially with each oral dissent. In another oral dissent, Ginsburg quoted a familiar Martin Luther King Jr. line, adding her coda:” ‘The arc of the universe is long, but it bends toward justice,’” but only “if there is a steadfast commitment to see the task through to completion.” …
Martin Luther King Jr. popularized and paraphrased the quote (from a January 18, 2018 article by Mychal Denzel Smith for Huffington Post),
His use of the quote is best understood by considering his source material. “The arc of the moral universe is long, but it bends toward justice” is King’s clever paraphrasing of a portion of a sermon delivered in 1853 by the abolitionist minister Theodore Parker. Born in Lexington, Massachusetts, in 1810, Parker studied at Harvard Divinity School and eventually became an influential transcendentalist and minister in the Unitarian church. In that sermon, Parker said: “I do not pretend to understand the moral universe. The arc is a long one. My eye reaches but little ways. I cannot calculate the curve and complete the figure by experience of sight. I can divine it by conscience. And from what I see I am sure it bends toward justice.”
I choose to keep faith that people will get the healthcare products they need and that all of us need to keep working at making access more fair.
Researchers at Stanford University (California, US) believe they have a solution for a problem with neuroprosthetics (Note: I have included brief comments about neuroprosthetics and possible ethical issues at the end of this posting) according an August 5, 2020 news item on ScienceDaily,
The current generation of neural implants record enormous amounts of neural activity, then transmit these brain signals through wires to a computer. But, so far, when researchers have tried to create wireless brain-computer interfaces to do this, it took so much power to transmit the data that the implants generated too much heat to be safe for the patient. A new study suggests how to solve his problem — and thus cut the wires.
Stanford researchers have been working for years to advance a technology that could one day help people with paralysis regain use of their limbs, and enable amputees to use their thoughts to control prostheses and interact with computers.
The team has been focusing on improving a brain-computer interface, a device implanted beneath the skull on the surface of a patient’s brain. This implant connects the human nervous system to an electronic device that might, for instance, help restore some motor control to a person with a spinal cord injury, or someone with a neurological condition like amyotrophic lateral sclerosis, also called Lou Gehrig’s disease.
The current generation of these devices record enormous amounts of neural activity, then transmit these brain signals through wires to a computer. But when researchers have tried to create wireless brain-computer interfaces to do this, it took so much power to transmit the data that the devices would generate too much heat to be safe for the patient.
Now, a team led by electrical engineers and neuroscientists Krishna Shenoy, PhD, and Boris Murmann, PhD, and neurosurgeon and neuroscientist Jaimie Henderson, MD, have shown how it would be possible to create a wireless device, capable of gathering and transmitting accurate neural signals, but using a tenth of the power required by current wire-enabled systems. These wireless devices would look more natural than the wired models and give patients freer range of motion.
Graduate student Nir Even-Chen and postdoctoral fellow Dante Muratore, PhD, describe the team’s approach in a Nature Biomedical Engineering paper.
The team’s neuroscientists identified the specific neural signals needed to control a prosthetic device, such as a robotic arm or a computer cursor. The team’s electrical engineers then designed the circuitry that would enable a future, wireless brain-computer interface to process and transmit these these carefully identified and isolated signals, using less power and thus making it safe to implant the device on the surface of the brain.
To test their idea, the researchers collected neuronal data from three nonhuman primates and one human participant in a (BrainGate) clinical trial.
As the subjects performed movement tasks, such as positioning a cursor on a computer screen, the researchers took measurements. The findings validated their hypothesis that a wireless interface could accurately control an individual’s motion by recording a subset of action-specific brain signals, rather than acting like the wired device and collecting brain signals in bulk.
The next step will be to build an implant based on this new approach and proceed through a series of tests toward the ultimate goal.
As I found out while investigating, ethical issues in this area abound. My first thought was to look at how someone with a focus on ability studies might view the complexities.
My ‘go to’ resource for human enhancement and ethical issues is Gregor Wolbring, an associate professor at the University of Calgary (Alberta, Canada). his profile lists these areas of interest: ability studies, disability studies, governance of emerging and existing sciences and technologies (e.g. neuromorphic engineering, genetics, synthetic biology, robotics, artificial intelligence, automatization, brain machine interfaces, sensors) and more.
I can’t find anything more recent on this particular topic but I did find an August 10, 2017 essay for The Conversation where he comments on technology and human enhancement ethical issues where the technology is gene-editing. Regardless, he makes points that are applicable to brain-computer interfaces (human enhancement), Note: Links have been removed),
Ability expectations have been and still are used to disable, or disempower, many people, not only people seen as impaired. They’ve been used to disable or marginalize women (men making the argument that rationality is an important ability and women don’t have it). They also have been used to disable and disempower certain ethnic groups (one ethnic group argues they’re smarter than another ethnic group) and others.
A recent Pew Research survey on human enhancement revealed that an increase in the ability to be productive at work was seen as a positive. What does such ability expectation mean for the “us” in an era of scientific advancements in gene-editing, human enhancement and robotics?
Which abilities are seen as more important than others?
The ability expectations among “us” will determine how gene-editing and other scientific advances will be used.
And so how we govern ability expectations, and who influences that governance, will shape the future. Therefore, it’s essential that ability governance and ability literacy play a major role in shaping all advancements in science and technology.
One of the reasons I find Gregor’s commentary so valuable is that he writes lucidly about ability and disability as concepts and poses what can be provocative questions about expectations and what it is to be truly abled or disabled. You can find more of his writing here on his eponymous (more or less) blog.
Ethics of clinical trials for testing brain implants
In 2003, neurologist Helen Mayberg of Emory University in Atlanta began to test a bold, experimental treatment for people with severe depression, which involved implanting metal electrodes deep in the brain in a region called area 25 [emphases mine]. The initial data were promising; eventually, they convinced a device company, St. Jude Medical in Saint Paul, to sponsor a 200-person clinical trial dubbed BROADEN.
This month [October 2017], however, Lancet Psychiatry reported the first published data on the trial’s failure. The study stopped recruiting participants in 2012, after a 6-month study in 90 people failed to show statistically significant improvements between those receiving active stimulation and a control group, in which the device was implanted but switched off.
… a tricky dilemma for companies and research teams involved in deep brain stimulation (DBS) research: If trial participants want to keep their implants [emphases mine], who will take responsibility—and pay—for their ongoing care? And participants in last week’s meeting said it underscores the need for the growing corps of DBS researchers to think long-term about their planned studies.
… participants bear financial responsibility for maintaining the device should they choose to keep it, and for any additional surgeries that might be needed in the future, Mayberg says. “The big issue becomes cost [emphasis mine],” she says. “We transition from having grants and device donations” covering costs, to patients being responsible. And although the participants agreed to those conditions before enrolling in the trial, Mayberg says she considers it a “moral responsibility” to advocate for lower costs for her patients, even it if means “begging for charity payments” from hospitals. And she worries about what will happen to trial participants if she is no longer around to advocate for them. “What happens if I retire, or get hit by a bus?” she asks.
There’s another uncomfortable possibility: that the hypothesis was wrong [emphases mine] to begin with. A large body of evidence from many different labs supports the idea that area 25 is “key to successful antidepressant response,” Mayberg says. But “it may be too simple-minded” to think that zapping a single brain node and its connections can effectively treat a disease as complex as depression, Krakauer [John Krakauer, a neuroscientist at Johns Hopkins University in Baltimore, Maryland] says. Figuring that out will likely require more preclinical research in people—a daunting prospect that raises additional ethical dilemmas, Krakauer says. “The hardest thing about being a clinical researcher,” he says, “is knowing when to jump.”
Brain-computer interfaces, symbiosis, and ethical issues
This was the most recent and most directly applicable work that I could find. From a July 24, 2019 article by Liam Drew for Nature Outlook: The brain,
“It becomes part of you,” Patient 6 said, describing the technology that enabled her, after 45 years of severe epilepsy, to halt her disabling seizures. Electrodes had been implanted on the surface of her brain that would send a signal to a hand-held device when they detected signs of impending epileptic activity. On hearing a warning from the device, Patient 6 knew to take a dose of medication to halt the coming seizure.
“You grow gradually into it and get used to it, so it then becomes a part of every day,” she told Frederic Gilbert, an ethicist who studies brain–computer interfaces (BCIs) at the University of Tasmania in Hobart, Australia. “It became me,” she said. [emphasis mine]
Gilbert was interviewing six people who had participated in the first clinical trial of a predictive BCI to help understand how living with a computer that monitors brain activity directly affects individuals psychologically1. Patient 6’s experience was extreme: Gilbert describes her relationship with her BCI as a “radical symbiosis”.
Symbiosis is a term, borrowed from ecology, that means an intimate co-existence of two species for mutual advantage. As technologists work towards directly connecting the human brain to computers, it is increasingly being used to describe humans’ potential relationship with artificial intelligence.
Interface technologies are divided into those that ‘read’ the brain to record brain activity and decode its meaning, and those that ‘write’ to the brain to manipulate activity in specific regions and affect their function.
Commercial research is opaque, but scientists at social-media platform Facebook are known to be pursuing brain-reading techniques for use in headsets that would convert users’ brain activity into text. And neurotechnology companies such as Kernel in Los Angeles, California, and Neuralink, founded by Elon Musk in San Francisco, California, predict bidirectional coupling in which computers respond to people’s brain activity and insert information into their neural circuitry. [emphasis mine]
Already, it is clear that melding digital technologies with human brains can have provocative effects, not least on people’s agency — their ability to act freely and according to their own choices. Although neuroethicists’ priority is to optimize medical practice, their observations also shape the debate about the development of commercial neurotechnologies.
Neuroethicists began to note the complex nature of the therapy’s side effects. “Some effects that might be described as personality changes are more problematic than others,” says Maslen [Hannah Maslen, a neuroethicist at the University of Oxford, UK]. A crucial question is whether the person who is undergoing stimulation can reflect on how they have changed. Gilbert, for instance, describes a DBS patient who started to gamble compulsively, blowing his family’s savings and seeming not to care. He could only understand how problematic his behaviour was when the stimulation was turned off.
Such cases present serious questions about how the technology might affect a person’s ability to give consent to be treated, or for treatment to continue. [emphases mine] If the person who is undergoing DBS is happy to continue, should a concerned family member or doctor be able to overrule them? If someone other than the patient can terminate treatment against the patient’s wishes, it implies that the technology degrades people’s ability to make decisions for themselves. It suggests that if a person thinks in a certain way only when an electrical current alters their brain activity, then those thoughts do not reflect an authentic self.
To observe a person with tetraplegia bringing a drink to their mouth using a BCI-controlled robotic arm is spectacular. [emphasis mine] This rapidly advancing technology works by implanting an array of electrodes either on or in a person’s motor cortex — a brain region involved in planning and executing movements. The activity of the brain is recorded while the individual engages in cognitive tasks, such as imagining that they are moving their hand, and these recordings are used to command the robotic limb.
If neuroscientists could unambiguously discern a person’s intentions from the chattering electrical activity that they record in the brain, and then see that it matched the robotic arm’s actions, ethical concerns would be minimized. But this is not the case. The neural correlates of psychological phenomena are inexact and poorly understood, which means that signals from the brain are increasingly being processed by artificial intelligence (AI) software before reaching prostheses.[emphasis mine]
But, he [Philipp Kellmeyer, a neurologist and neuroethicist at the University of Freiburg, Germany] says, using AI tools also introduces ethical issues of which regulators have little experience. [emphasis mine] Machine-learning software learns to analyse data by generating algorithms that cannot be predicted and that are difficult, or impossible, to comprehend. This introduces an unknown and perhaps unaccountable process between a person’s thoughts and the technology that is acting on their behalf.
Maslen is already helping to shape BCI-device regulation. She is in discussion with the European Commission about regulations it will implement in 2020 that cover non-invasive brain-modulating devices that are sold straight to consumers. [emphases mine; Note: There is a Canadian company selling this type of product, MUSE] Maslen became interested in the safety of these devices, which were covered by only cursory safety regulations. Although such devices are simple, they pass electrical currents through people’s scalps to modulate brain activity. Maslen found reports of them causing burns, headaches and visual disturbances. She also says clinical studies have shown that, although non-invasive electrical stimulation of the brain can enhance certain cognitive abilities, this can come at the cost of deficits in other aspects of cognition.
Regarding my note about MUSE, the company is InteraXon and its product is MUSE.They advertise the product as “Brain Sensing Headbands That Improve Your Meditation Practice.” The company website and the product seem to be one entity, Choose Muse. The company’s product has been used in some serious research papers they can be found here. I did not see any research papers concerning safety issues.
It’s easy to forget that in all the excitement over technologies ‘making our lives better’ that there can be a dark side or two. Some of the points brought forth in the articles by Wolbring, Underwood, and Drew confirmed my uneasiness as reasonable and gave me some specific examples of how these technologies raise new issues or old issues in new ways.
What I find interesting is that no one is using the term ‘cyborg’, which would seem quite applicable.There is an April 20, 2012 posting here titled ‘My mother is a cyborg‘ where I noted that by at lease one definition people with joint replacements, pacemakers, etc. are considered cyborgs. In short, cyborgs or technology integrated into bodies have been amongst us for quite some time.
Interestingly, no one seems to care much when insects are turned into cyborgs (can’t remember who pointed this out) but it is a popular area of research especially for military applications and search and rescue applications.
I’ve sometimes used the term ‘machine/flesh’ and or ‘augmentation’ as a description of technologies integrated with bodies, human or otherwise. You can find lots on the topic here however I’ve tagged or categorized it.
Amongst other pieces you can find here, there’s the August 8, 2016 posting, ‘Technology, athletics, and the ‘new’ human‘ featuring Oscar Pistorius when he was still best known as the ‘blade runner’ and a remarkably successful paralympic athlete. It’s about his efforts to compete against able-bodied athletes at the London Olympic Games in 2012. It is fascinating to read about technology and elite athletes of any kind as they are often the first to try out ‘enhancements’.
Gregor Wolbring has a number of essays on The Conversation looking at Paralympic athletes and their pursuit of enhancements and how all of this is affecting our notions of abilities and disabilities. By extension, one has to assume that ‘abled’ athletes are also affected with the trickle-down effect on the rest of us.
Regardless of where we start the investigation, there is a sameness to the participants in neuroethics discussions with a few experts and commercial interests deciding on how the rest of us (however you define ‘us’ as per Gregor Wolbring’s essay) will live.
This paucity of perspectives is something I was getting at in my COVID-19 editorial for the Canadian Science Policy Centre. My thesis being that we need a range of ideas and insights that cannot be culled from small groups of people who’ve trained and read the same materials or entrepreneurs who too often seem to put profit over thoughtful implementations of new technologies. (See the PDF May 2020 edition [you’ll find me under Policy Development]) or see my May 15, 2020 posting here (with all the sources listed.)
As for this new research at Stanford, it’s exciting news, which raises questions, as it offers the hope of independent movement for people diagnosed as tetraplegic (sometimes known as quadriplegic.)
The line between life and death may not be what we thought it was according to some research that was reported in April 2019. Ed Wong’s April 17, 2019 article (behind a paywall) for The Atlantic was my first inkling about the life-death questions raised by some research performed at Yale University, (Note: Links have been removed)
The brain, supposedly, cannot long survive without blood. Within seconds, oxygen supplies deplete, electrical activity fades, and unconsciousness sets in. If blood flow is not restored, within minutes, neurons start to die in a rapid, irreversible, and ultimately fatal wave.
But maybe not? According to a team of scientists led by Nenad Sestan at Yale School of Medicine, this process might play out over a much longer time frame, and perhaps isn’t as inevitable or irreparable as commonly believed. Sestan and his colleagues showed this in dramatic fashion—by preserving and restoring signs of activity in the isolated brains of pigs that had been decapitated four hours earlier.
The team sourced 32 pig brains from a slaughterhouse, placed them in spherical chambers, and infused them with nutrients and protective chemicals, using pumps that mimicked the beats of a heart. This system, dubbed BrainEx, preserved the overall architecture of the brains, preventing them from degrading. It restored flow in their blood vessels, which once again became sensitive to dilating drugs. It stopped many neurons and other cells from dying, and reinstated their ability to consume sugar and oxygen. Some of these rescued neurons even started to fire. “Everything was surprising,” says Zvonimir Vrselja, who performed most of the experiments along with Stefano Daniele.
… “I don’t see anything in this report that should undermine confidence in brain death as a criterion of death,” says Winston Chiong, a neurologist at the University of California at San Francisco. The matter of when to declare someone dead has become more controversial since doctors began relying more heavily on neurological signs, starting around 1968, when the criteria for “brain death” were defined. But that diagnosis typically hinges on the loss of brainwide activity—a line that, at least for now, is still final and irreversible. After MIT Technology Review broke the news of Sestan’s work a year ago, he started receiving emails from people asking whether he could restore brain function to their loved ones. He very much cannot. BrainEx isn’t a resurrection chamber.
“It’s not going to result in human brain transplants,” adds Karen Rommelfanger, who directs Emory University’s neuroethics program. “And I don’t think this means that the singularity is coming, or that radical life extension is more possible than before.”
So why do the study? “There’s potential for using this method to develop innovative treatments for patients with strokes or other types of brain injuries, and there’s a real need for those kinds of treatments,” says L. Syd M Johnson, a neuroethicist at Michigan Technological University. The BrainEx method might not be able to fully revive hours-dead brains, but Yama Akbari, a critical-care neurologist at the University of California at Irvine, wonders whether it would be more successful if applied minutes after death. Alternatively, it could help to keep oxygen-starved brains alive and intact while patients wait to be treated. “It’s an important landmark study,” Akbari says.
Yong notes that the study still needs to be replicated in his article which also probes some of the ethical issues associated with the latest neuroscience research.
Nature published the Yale study,
Restoration of brain circulation and cellular functions hours post-mortem by Zvonimir Vrselja, Stefano G. Daniele, John Silbereis, Francesca Talpo, Yury M. Morozov, André M. M. Sousa, Brian S. Tanaka, Mario Skarica, Mihovil Pletikos, Navjot Kaur, Zhen W. Zhuang, Zhao Liu, Rafeed Alkawadri, Albert J. Sinusas, Stephen R. Latham, Stephen G. Waxman & Nenad Sestan. Nature 568, 336–343 (2019) DOI: https://doi.org/10.1038/s41586-019-1099-1 Published 17 April 2019 Issue Date 18 April 2019
The brain is more resilient than previously thought. In a groundbreaking experiment published in this week’s issue of Nature, neuroscientists created an artificial circulation system that successfully restored some functions and structures in donated pig brains–up to four hours after the pigs were butchered at a USDA food processing facility. Though there was no evidence of restored consciousness, brains from the pigs were without oxygen for hours, yet could still support key functions provided by the artificial system. The result challenges the notion that mammalian brains are fully and irreversibly damaged by a lack of oxygen.
“The assumptions have always been that after a couple minutes of anoxia, or no oxygen, the brain is ‘dead,'” says Stuart Youngner, MD, who co-authored a commentary accompanying the study with Insoo Hyun, PhD, both professors in the Department of Bioethics at Case Western Reserve University School of Medicine. “The system used by the researchers begs the question: How long should we try to save people?”
In the pig experiment, researchers used an artificial perfusate (a type of cell-free “artificial blood”), which helped brain cells maintain their structure and some functions. Resuscitative efforts in humans, like CPR, are also designed to get oxygen to the brain and stave off brain damage. After a period of time, if a person doesn’t respond to resuscitative efforts, emergency medical teams declare them dead.
The acceptable duration of resuscitative efforts is somewhat uncertain. “It varies by country, emergency medical team, and hospital,” Youngner said. Promising results from the pig experiment further muddy the waters about the when to stop life-saving efforts.
At some point, emergency teams must make a critical switch from trying to save a patient, to trying to save organs, said Youngner. “In Europe, when emergency teams stop resuscitation efforts, they declare a patient dead, and then restart the resuscitation effort to circulate blood to the organs so they can preserve them for transplantation.”
The switch can involve extreme means. In the commentary, Youngner and Hyun describe how some organ recovery teams use a balloon to physically cut off blood circulation to the brain after declaring a person dead, to prepare the organs for transplantation.
The pig experiment implies that sophisticated efforts to perfuse the brain might maintain brain cells. If technologies like those used in the pig experiment could be adapted for humans (a long way off, caution Youngner and Hyun), some people who, today, are typically declared legally dead after a catastrophic loss of oxygen could, tomorrow, become candidates for brain resuscitation, instead of organ donation.
Said Youngner, “As we get better at resuscitating the brain, we need to decide when are we going to save a patient, and when are we going to declare them dead–and save five or more who might benefit from an organ.”
Because brain resuscitation strategies are in their infancy and will surely trigger additional efforts, the scientific and ethics community needs to begin discussions now, says Hyun. “This study is likely to raise a lot of public concerns. We hoped to get ahead of the hype and offer an early, reasoned response to this scientific advance.”
Both Youngner and Hyun praise the experiment as a “major scientific advancement” that is overwhelmingly positive. It raises the tantalizing possibility that the grave risks of brain damage caused by a lack of oxygen could, in some cases, be reversible. “Pig brains are similar in many ways to human brains, which makes this study so compelling,” Hyun said. “We urge policymakers to think proactively about what this line of research might mean for ongoing debates around organ donation and end of life care.”
Here’s a link to and a citation to the Nature commentary,
This research will not find itself occupying anyone’s brain for some time to come but it is interesting to find out that neural prosthetics have some drawbacks and there is work being done to address them. From an Aug. 10, 2015 news item on Azonano,
Instead of using neural prosthetic devices–which suffer from immune-system rejection and are believed to fail due to a material and mechanical mismatch–a multi-institutional team, including Lohitash Karumbaiah of the University of Georgia’s Regenerative Bioscience Center, has developed a brain-friendly extracellular matrix environment of neuronal cells that contain very little foreign material. These by-design electrodes are shielded by a covering that the brain recognizes as part of its own composition.
Although once believed to be devoid of immune cells and therefore of immune responses, the brain is now recognized to have its own immune system that protects it against foreign invaders.
“This is not by any means the device that you’re going to implant into a patient,” said Karumbaiah, an assistant professor of animal and dairy science in the UGA College of Agricultural and Environmental Sciences. “This is proof of concept that extracellular matrix can be used to ensheathe a functioning electrode without the use of any other foreign or synthetic materials.”
Implantable neural prosthetic devices in the brain have been around for almost two decades, helping people living with limb loss and spinal cord injury become more independent. However, not only do neural prosthetic devices suffer from immune-system rejection, but most are believed to eventually fail because of a mismatch between the soft brain tissue and the rigid devices.
The collaboration, led by Wen Shen and Mark Allen of the University of Pennsylvania, found that the extracellular matrix derived electrodes adapted to the mechanical properties of brain tissue and were capable of acquiring neural recordings from the brain cortex.
“Neural interface technology is literally mind boggling, considering that one might someday control a prosthetic limb with one’s own thoughts,” Karumbaiah said.
The study’s joint collaborators were Ravi Bellamkonda, who conceived the new approach and is chair of the Wallace H. Coulter Department of Biomedical Engineering at the Georgia Institute of Technology and Emory University, as well as Allen, who at the time was director of the Institute for Electronics and Nanotechnology.
“Hopefully, once we converge upon the nanofabrication techniques that would enable these to be clinically translational, this same methodology could then be applied in getting these extracellular matrix derived electrodes to be the next wave of brain implants,” Karumbaiah said.
Currently, one out of every 190 Americans is living with limb loss, according to the National Institutes of Health. There is a significant burden in cost of care and quality of life for people suffering from this disability.
The research team is one part of many in the prosthesis industry, which includes those who design the robotics for the artificial limbs, others who make the neural prosthetic devices and developers who design the software that decodes the neural signal.
“What neural prosthetic devices do is communicate seamlessly to an external prosthesis,” Karumbaiah said, “providing independence of function without having to have a person or a facility dedicated to their care.”
Karumbaiah hopes further collaboration will allow them to make positive changes in the industry, saying that, “it’s the researcher-to-industry kind of conversation that now needs to take place, where companies need to come in and ask: ‘What have you learned? How are the devices deficient, and how can we make them better?'”
One final note, I have written frequently about prosthetics and neural prosthetics, which you can find by using either of those terms and/or human enhancement. Here’s my latest piece, a March 25, 2015 posting.
As a writer I love to believe my words have a lasting impact and while this research is focused on fiction, something I write more rarely than nonfiction, hope springs eternal that one day nonfiction too will be proved as having an impact (in a good way) on the brain. From a Jan. 3, 2014 news release on EurekAlert (or you can read the Dec. 17, 2013 Emory University news release by Carol Clark),
Many people can recall reading at least one cherished story that they say changed their life. Now researchers at Emory University have detected what may be biological traces related to this feeling: Actual changes in the brain that linger, at least for a few days, after reading a novel.
“Stories shape our lives and in some cases help define a person,” says neuroscientist Gregory Berns, lead author of the study and the director of Emory’s Center for Neuropolicy. “We want to understand how stories get into your brain, and what they do to it.”
His co-authors included Kristina Blaine and Brandon Pye from the Center for Neuropolicy, and Michael Prietula from Emory’s Goizueta Business School.
Neurobiological research using functional magnetic resonance imaging (fMRI) has begun to identify brain networks associated with reading stories. Most previous studies have focused on the cognitive processes involved in short stories, while subjects are actually reading them while they are in the fMRI scanner.
All of the study subjects read the same novel, “Pompeii,” a 2003 thriller by Robert Harris that is based on the real-life eruption of Mount Vesuvius in ancient Italy.
“The story follows a protagonist, who is outside the city of Pompeii and notices steam and strange things happening around the volcano,” Berns says. “He tries to get back to Pompeii in time to save the woman he loves. Meanwhile, the volcano continues to bubble and nobody in the city recognizes the signs.”
The researchers chose the book due to its page-turning plot. “It depicts true events in a fictional and dramatic way,” Berns says. “It was important to us that the book had a strong narrative line.”
For the first five days, the participants came in each morning for a base-line fMRI scan of their brains in a resting state. Then they were fed nine sections of the novel, about 30 pages each, over a nine-day period. They were asked to read the assigned section in the evening, and come in the following morning. After taking a quiz to ensure they had finished the assigned reading, the participants underwent an fMRI scan of their brain in a non-reading, resting state. After completing all nine sections of the novel, the participants returned for five more mornings to undergo additional scans in a resting state.
The results showed heightened connectivity in the left temporal cortex, an area of the brain associated with receptivity for language, on the mornings following the reading assignments. “Even though the participants were not actually reading the novel while they were in the scanner, they retained this heightened connectivity,” Berns says. “We call that a ‘shadow activity,’ almost like a muscle memory.”
Heightened connectivity was also seen in the central sulcus of the brain, the primary sensory motor region of the brain. Neurons of this region have been associated with making representations of sensation for the body, a phenomenon known as grounded cognition. Just thinking about running, for instance, can activate the neurons associated with the physical act of running.
“The neural changes that we found associated with physical sensation and movement systems suggest that reading a novel can transport you into the body of the protagonist,” Berns says. “We already knew that good stories can put you in someone else’s shoes in a figurative sense. Now we’re seeing that something may also be happening biologically.”
The neural changes were not just immediate reactions, Berns says, since they persisted the morning after the readings, and for the five days after the participants completed the novel.
“It remains an open question how long these neural changes might last,” Berns says. “But the fact that we’re detecting them over a few days for a randomly assigned novel suggests that your favorite novels could certainly have a bigger and longer-lasting effect on the biology of your brain.”
This is an open access paper where you’ll notice the participants cover a narrow range of ages (from the Materials and Methods section of the paper,
A total of 21 participants were studied. Two were excluded from the fMRI analyses: one for insufficient attendance, and the other for image abnormalities. Before the experiment, participants were screened for the presence of medical and psychiatric diagnoses, and none were taking medications. There were 12 female and 9 male participants between the ages of 19 and 27 (mean 21.5). Emory University’s Institutional Review Board approved all procedures, and all participants gave written informed consent.
It’s always good to remember that university research often draws from student populations and the question one might want to ask is whether or not those results will remain the same, more or less, throughout someone’s life span.In any event, I find this research intriguing and hope they follow this up.
Currently known as the BRAIN (Brain Research through Advancing Innovative Neurotechnologies), I first wrote about the project under its old name BAM (Brain Activity Map) in two postings, first in a March 4, 2013 posting featuring brain-to-brain communication and other brain-related tidbits, then again, in an April 2, 2013 posting featuring an announcement about its federal funding. Today (Jan. 6, 2014), I stumbled across some BRAIN funding opportunities for researchers, from the BRAIN Initiative funding opportunities webpage,
NIH released six funding opportunity announcements in support of the President’s BRAIN Initiative. Collectively, these opportunities focus on building a new arsenal of tools and technologies for helping scientists unlock the mysteries of the brain. NIH [US National Institutes of Health] plans to invest $40 million in Fiscal Year 2014 through these opportunities, contingent upon the submission of a sufficient number of scientifically meritorious applications.
The opportunities currently available are as follows:
Transformative Approaches for Cell-Type Classification in the Brain (U01) (RFA-MH-14-215) – aims to pilot classification strategies to generate a systematic inventory/cell census of cell types in the brain, integrating molecular identity of cell types with connectivity, morphology, and location. These pilot projects and methodologies should be designed to demonstrate their utility and scalability to ultimately complete a comprehensive cell census of the human brain. Contact Email:BRAIN-info-NIMH@mail.nih.gov Application Receipt: March 13, 2014
Development and Validation of Novel Tools to Analyze Cell-Specific and Circuit-Specific Processes in the Brain (U01) (RFA-MH-14-216) – aims to develop and validate novel tools that possess a high degree of cell-type and/or circuit-level specificity to facilitate the detailed analysis of complex circuits and provide insights into cellular interactions that underlie brain function. A particular emphasis is the development of new genetic and non-genetic tools for delivering genes, proteins and chemicals to cells of interest; new approaches are also expected to target specific cell types and or circuits in the nervous system with greater precision and sensitivity than currently established methods. Contact Email:BRAIN-info-NIMH@mail.nih.gov Application Receipt: March 13, 2014
New Technologies and Novel Approaches for Large-Scale Recording and Modulation in the Nervous System (U01) (RFA-NS-14-007) – focuses on development and proof-of-concept testing of new technologies and novel approaches for large scale recording and manipulation of neural activity, with cellular resolution, at multiple spatial and/or temporal scales, in any region and throughout the entire depth of the brain. The proposed research may be high risk, but if successful could profoundly change the course of neuroscience research. Contact Email:NINDS-Brain-Initiative@nih.gov Application Receipt: March 24, 2014
Optimization of Transformative Technologies for Large Scale Recording and Modulation in the Nervous System (U01) (RFA-NS-14-008) – aims to optimize existing and emerging technologies and approaches that have the potential to address major challenges associated with recording and manipulating neural activity. This FOA is intended for the iterative refinement of emergent technologies and approaches that have already demonstrated their transformative potential through initial proof-of-concept testing, and are appropriate for accelerated engineering development with an end-goal of broad dissemination and incorporation into regular neuroscience research. Contact Email:NINDS-Brain-Initiative@nih.gov Application Receipt: March 24, 2014
Integrated Approaches to Understanding Circuit Function in the Nervous System (U01) (RFA-NS-14-009) – focuses onexploratory studies that use new and emerging methods for large scale recording and manipulation to elucidate the contributions of dynamic circuit activity to a specific behavioral or neural system. Applications should propose teams of investigators that seek to cross boundaries of interdisciplinary collaboration, for integrated development of experimental, analytic and theoretical capabilities in preparation for a future competition for large-scale awards. Contact Email:NINDS-Brain-Initiative@nih.gov Application Receipt: March 24, 2014
Planning for Next Generation Human Brain Imaging (R24) (RFA-MH-14-217) – aims to create teams of imaging scientist together with other experts from a range of disciplines such as engineering, material sciences, nanotechnology and computer science, to plan for a new generation of non-invasive imaging techniques that would be used to understand human brain function. Incremental improvements to existing technologies will not be funded under this announcement. Contact Email:firstname.lastname@example.org Application Receipt: March 13, 2014
For the interested, in the near future there will be some informational conference calls regarding these opportunities,
Informational Conference Calls for Prospective Applicants
NIH will be hosting a series of informational conference calls to address technical questions regarding applications to each of the RFAs released under the BRAIN Initiative. Information on dates and contacts for each of the conference calls is as follows:
January 10, 2014, 2:00-3:00 PM EST RFA-MH-14-215, Transformative Approaches for Cell-Type Classification in the Brain
February 4, 2014, 1:00-2:30 PM EST RFA-NS-14-007, New Technologies and Novel Approaches for Large-Scale Recording and Modulation in the Nervous System RFA-NS-14-008, Optimization of Transformative Technologies for Large Scale Recording and Modulation in the Nervous System RFA-NS-14-009, Integrated Approaches to Understanding Circuit Function in the Nervous System
For call-in information, contact Karen David at NINDS-Brain-Initiative@nih.gov.
In addition to accessing the information provided in the upcoming conference calls, applicants are strongly encouraged to consult with the Scientific/Research Contacts listed in each of the RFAs to discuss the alignment of their proposed work with the goals of the RFA to which they intend to apply.
It’s kind of fascinating to see this much emphasis on brains what with the BRAIN Initiative in the US and the Human Brain Project in Europe (my Jan. 28, 2013 posting announcing the European Union’s winning Future and Emerging Technologies (FET) research projects, The prizes (1B Euros to be paid out over 10 years to each winner) had been won by the Human Brain FET project and the Graphene FET project, respectively
As I have noted before (most recently in a Feb. 13, 2013 posting) there are at least two Grand Challenges, one is a Bill & Melinda Gates Foundation program and the other, Grand Challenges Canada, is funded by the Canadian government. Both organizations along with the U.S. Agency for International Development (USAID), the Government of Norway, and the U.K’s Department for International Development (DFID) have combined their efforts on maternal health in a partnership, Saving Lives at Birth: A Grand Challenge for Development. 2013 is the third year for this competitive funding program, which attracts entries from around the world.
The organization’s July 31, 2013 news release announces the latest funding nominees,
The Saving Lives at Birth: A Grand Challenge for Development today announced 22 Round 3 award nominees from a pool of 53 finalists – innovators who descended on Washington for three days (DevelopmentXChange) to showcase bold, new ideas to save the lives of mothers and newborns in developing countries with aspirations of international funding to realize their vision.
The award nominees cut across maternal and neonatal health, family planning, nutrition and HIV and they present not only cutting-edge technologies that can be used in resource-poor settings, but innovative approaches to delivering services and the adoption of healthy behaviors. The announcement was made at the closing forum of the DevelopmentXChange by the Saving Lives at Birth partners. The nominees will now enter into final negotiations before awards are issued. [emphasis mine]
If I read this rightly, the nominees do not receive a set amount but negotiate for the money they need to implement and/or develop their ‘solution’. The news release provides more details about the process that applicants undertake when they reach the finalist stage,
The Saving Lives at Birth DevelopmentXChange provided a platform for top global innovators to present their ideas in an open, dynamic marketplace and exchange ideas with development experts and potential funders to help meet the immense challenge of protecting mothers and newborns in the poorest places on earth, during their most vulnerable hours. Other promising ideas will be considered for “incubator awards” to assist innovators in further developing their ideas through dialogue and mentorship.
The Saving Lives at Birth DevelopmentXChange featured discussions focused on meeting the needs and realities of women and children in low-resource settings as well as workshops that explored business planning, market research, impact investing, and strategies for scaling their innovations. The three-day event concluded with a forum featuring Ambassador Susan E. Rice, National Security Advisor; Dr. Rajiv Shah, Administrator, USAID; HRH Princess Sarah Zeid of Jordan; New York Times best-selling author Dan Heath and NASA astronaut Col. Ron Garan (ret.).
Leading into the DevelopmentXChange, existing Saving Lives at Birth grantees participated in a three-day, customized training program – a focal point of the global health Xcelerator. This eight-month program, offered through a partnership between National Collegiate Inventors and Innovators Alliance (NCIIA), the Lemelson Foundation and USAID, provides grantees the tools and knowledge to scale their ideas and maximize the impact of their innovations.
Here’s the list of nominees who emerged from the process (there is one overtly nanotechnology project listed and I suspect others are also enabled by nanotechnology),
Award nominees of Saving Lives at Birth Round 3 include 4 transition-to-scale grant nominees:
· Africare – Dakar, Senegal: A collaborative community-based technology that integrates community support services with mobile and telemedicine platforms to increase demand for, and access to, quality prenatal care services in Senegal. More: http://savinglivesatbirth.net/summaries/232
· Epidemiological Research Center in Sexual and Reproductive Health – Guatemala City, Guatemala: An integrated approach to reduce maternal and perinatal mortality in Northern Guatemala through simulation-based training, social marketing campaigns and formal health care system engagement. More: http://savinglivesatbirth.net/summaries/246
· Massachusetts General Hospital – Boston, MA, USA: A next-generation uterine balloon tamponade (UBT) device to treat postpartum hemorrhage (PPH) in Kenya and South Sudan. More: http://savinglivesatbirth.net/summaries/255
· The Research Institute at Nationwide Children’s Hospital – Columbus, OH, USA: A low-cost paper-based urine test for early diagnosis of pre-eclampsia to reduce pre-eclampsia morbidity and mortality in resource-limited areas. http://savinglivesatbirth.net/summaries/275
And 18 seed grant nominees:
· BILIMETRIX SRL – Trieste, Italy: An inexpensive system to rapidly test for markers of hyperbilirubinemia (kernicterus)-an often fatal form of brain damage caused by excessive jaundice- in low resource settings in Nigeria, Egypt, and Indonesia. More: http://savinglivesatbirth.net/summaries/235
· JustMilk – Dept. of Chemical Engineering, University of Cambridge – Cambridge, UK: A low-cost system that aids the administration of drugs and nutrients to breastfeeding infants via easily disintegrating tablets housed within a modified Nipple Shield Delivery System (NSDS). http://savinglivesatbirth.net/summaries/241
· The University of Melbourne – Melbourne, Australia: A low-cost, electricity-free oxygen concentrator suitable for providing provisional oxygen for neonates in low-resource settings. http://savinglivesatbirth.net/summaries/277
· University of Toronto – Toronto, Canada: A spray-encapsulated iron premix that will be attached to tea leaves to reduce rates of iron deficiency of pregnant women in South Asia. http://savinglivesatbirth.net/summaries/279
· Mbarara University of Science and Technology – Mbarara, Uganda: The Augmented Infant Resuscitator (AIR) which gives instant feedback to healthcare professionals performing newborn resuscitation to reduce neonatal deaths from intrapartum birth asphyxia or prematurity. http://savinglivesatbirth.net/summaries/256
· Bioceptive, Inc. – New Orleans, LA, USA: A low-cost, reusable, and intuitive intrauterine device (IUD) inserter to make the IUD insertion procedure easier and safer in low-resource settings. http://savinglivesatbirth.net/summaries/236
· Convergent Engineering Inc. – Newberry, FL, USA: An inexpensive, easy-to-use, handheld early-warning system that detects pre-eclampsia 10-12 weeks before the onset symptoms. The system pairs a wrist strap embedded with inexpensive ECG and photoplethysmography sensors with a smart phone for processing, data aggregation, and communication. http://savinglivesatbirth.net/summaries/239
· Dimagi, Inc. (CommTrack) – Cambridge, MA, USA: An open-source distribution management system integrating mobile and GPS technology to improve transparency, supply chain functioning, communication, and the timely delivery of medicine to hard to reach, low-income areas in Africa. http://savinglivesatbirth.net/summaries/243
· Duke University– Durham, NC, USA: Healthcare system integration of the “Pratt Pouch”-a tiny ketchup-like packet that stores antiretroviral AIDS medication for a year-to enable the pouch to be used in home-birth settings to prevent transmission of HIV from mother to child. Testing taking place in Zambia. http://savinglivesatbirth.net/summaries/244
· Emory University – Atlanta, GA, USA: A micro-needle patch that co-administers the influenza and tetanus toxoid vaccines to pregnant mothers and children in developing countries. http://savinglivesatbirth.net/summaries/245
· Nanobiosym, Inc – Cambridge, MA, USA: A nanotech platform which enables rapid, accurate and mobile HIV diagnosis at point-of-care, allowing for timely treatment with antiretroviral therapy to reduce HIV-related mortality in infants in Rwanda. http://savinglivesatbirth.net/summaries/259
· Population Services International – Washington DC, USA: A new inserter for immediate postpartum intrauterine device (PPIUD) insertions to increase contraceptive uptake in developing countries. http://savinglivesatbirth.net/summaries/263
· The Board of Regents of the University of Wisconsin System – Madison, WI, USA: A Lactobacillus casei strain that enables the sustainable home production of beta-Carotene enriched dairy products for at-risk mothers and families in Southern Asia. http://savinglivesatbirth.net/summaries/272
While it’s not stated explicitly, the main focus for Saving Lives at Birth appears to be the continent of Africa as per this video animation which represents the organization’s goals and focus,
I have written about Iron Man 3 before (my May 11, 2012 posting) in the context of its nanotechnology inspirations, specifically, the Extremis Armor. For anyone not familiar with the story, I have a few bits which will bring you up to speed before getting to Shuming Nie’s commentary and some recent research into injectable nano-networks, which seems highly relevant to the Iron Man 3 discourse. First, here’s an excerpt from my May 11, 2012 posting,
In a search for Extremis, I found out that this story reboots the Iron Man mythology by incorporating nanotechnology and alchemy to create a new armor, the Extremis Armor, from the Extremis Armor website (I strongly suggest going to the website and reading the full text which includes a number of illustrative images if you find this sort of thing interesting),
When a bio-tech weapon of mass destruction was unleashed, Tony Stark threw himself onto the bleeding edge between science and alchemy, combining nanotechnology and his Iron Man armor. The result, which debuted in Iron Man, Vol. IV, issue 5, was the Extremis Armor, Model XXXII, Mark I, which made him the most powerful hero in the world–but not without a price.
There were two key parts to this Extremis-enhanced suit. The first part is the golden Undersheath, the protective interface between Stark’s nervous system and the second chief part, the External Suit Devices (ESDs), a.k.a. the red armor plating.
The Undersheath to the Iron Man suit components was super-compressed and stored in the hollows of Stark’s bones. The sheath material exited through skeletal pores and slid between all cells to self-assemble a new “skin” around him. This skin provides a complete interface to the Iron Man suit components and can perform numerous other functions. (The process in reverse withdrew the Undersheath back into these specially modified areas of Tony Stark’s bone marrow tissue.)
The Undersheath is a nano-network that incorporates peptide-peptide logic (PPL), a molecular computational system made of superconducting plastic impregnated molecular chains. [my emphasis added for May.6.13 posting] The PPL handles, among other things: memory, critical logic paths, comparative “truth” tables, automatic response look-up tables, data storage, communication, and external sensing material interface.
The lattice assembly is a stress-compression truss with powered interstitial joints. This can surround the PPL material and guide it through Stark’s body. This steerable, motile lattice framework is commanded by the PPL molecule computational mentality. The metallic component to the lattice is a controlled mimetic artifact that can take on the characteristics of most elements. Even unusual combinations of behaviors such as extreme hardness and flexibility.
The combination of the two nano-scale materials allows for a very dense non-traditional computer that can change the fabric of its design in very powerful ways. The incorporation of the Undersheath in Stark’s entire nervous system renders reflex-level computer responses to pan-spectrum stimuli.
Anthony Stark’s Bio/Metalo-Mimetic Material concept is a radical departure from the traditional solid-state underpinnings of his prior Iron Man suit designs. Making use of nano-scale assembly technology, “smart” molecules can be made atom by atom. The design allows for simple computers to be linked into a massive parallel computer that synthesizes human thought protocols.
The External Suit Devices (ESDs), the red armor plates, were made via mega-nano technology that has assembled atoms into large, discreet effectors. This allows for the plates to be collapsable to very small volumes for easy storage and carried in Stark’s briefcase. The ESDs were commanded by the Undersheath and were self-powered by high-capacity Kasimer plates. They were equipped with large arrays of nano-fans that allow flight. Armoring-up was done by drawing the suit to Stark via a vectored repulsor field, just lightly pushing them from different angles.
The armor’s memory-metal technology renders it lightweight and flexible while not in use, but extremely durable when polarized. The armor was strong, of course, but it could be made even stronger by rerouting repulsor input to reinforce the armor’s mass.
Stark’s skin is now a part of the suit, when engaged. [emphasis mine] Comfort is relative because the suit rapidly responds to any discomfort, from impacts to high temperatures, from itching to scratching. The suit’s protocols include semi-autonomy when needed. Where Stark ends and the suit begins is flexible. The exact nature of the artificial Extremis Virus is not known (especially because Stark recompiled the dose, then tweaked the nutrients and suspended metals, radically altering Maya Hansen’s [the character Rebecca Hall will reputedly play] formulations). The effect it has had on Stark’s body is to allow the presence of so much alien material within his body without trauma.
Because of the bio-interface between Tony and the armor, he could utilize the suit to its fullest potential and also instantly access computers and any digital system worldwide at the speed of thought. He was biologically integrated with his armor, one with it, imbued with unprecedented powers and abilities. He channeled and processed data, emergency signals, and satellite reconnaissance from every law enforcement, military, and intelligence service in the world–in his head. He could send electronic signals and make phone calls with his mind. He could see through satellites. Plus he had the ability to transmit whatever he saw (from his visual cortex) to other people’s display screens. The computer’s cybernetic link enables him to operate all of the armor’s functions, as well as providing a remote link to other computers (as Stark is now part of the armor this connection is seamless). The armor’s system was connected to the global mainframe via StarkTech servers.
Extremis has been referred to as a “virus” constantly since the story. The verbatim description offered by its inventor Maya Hansen, goes: “…Extremis is a super-soldier solution. It’s a bio-electronics package, fitted into a few billion graphite nanotubes and suspended in a carrier fluid. [emphasis mine] A magic bullet, like the original super-soldier serum—all fitted into a single injection. It hacks the body’s repair center—the part of the brain that keeps a complete blue print of the human body. When we’re injured, we refer to that area of the brain to heal properly. Extremis rewrites the repair center. In the first stage, the body essentially becomes an open wound. The normal human blueprint is being replaced with the Extremis blueprint. The brain is being told the body is wrong. Extremis protocol dictates that the subject be placed on life support and intravenously fed nutrients at this point. For the next two or three days, the patient remains unconscious within a cocoon of scabs. (…) Extremis uses the nutrients and body mass to grow new organs. Better ones…”
Apparently, back in the early days of genetic engineering, a brilliant, zit-faced scientist (Guy Pearce) offered Tony a piece of a lucrative patent that had the potential to alter the human body, and even regenerate amputated limbs.
Tony walked away from the offer as well as the pretty girl (Rebecca Hall) who worked for the genetic engineer, but in the opening sequence, we see the technology was successfully developed and tested. It makes people superhuman, but it can also make them spontaneously combust, leaving great craters and human casualties behind.
Now for the video commentary, Dr. Shuming Nie, Biomedical Engineering at Emory University, offers some scientific insight into the science and the fiction of ‘extremis’ as per Iron Man 3 in his YouTube video,
Keeping on the science theme, researchers at North Carolina State University (NCSU) and other institutions announced an injectable nano-network for diabetics in a May 3, 2013 news release on EurekAlert,
In a promising development for diabetes treatment, researchers have developed a network of nanoscale particles that can be injected into the body and release insulin when blood-sugar levels rise, maintaining normal blood sugar levels for more than a week in animal-based laboratory tests. The work was done by researchers at North Carolina State University, the University of North Carolina at Chapel Hill, the Massachusetts Institute of Technology and Children’s Hospital Boston.
“We’ve created a ‘smart’ system that is injected into the body and responds to changes in blood sugar by releasing insulin, effectively controlling blood-sugar levels,” says Dr. Zhen Gu, lead author of a paper describing the work and an assistant professor in the joint biomedical engineering program at NC State and UNC Chapel Hill. “We’ve tested the technology in mice, and one injection was able to maintain blood sugar levels in the normal range for up to 10 days.”
Here’s how the smart system is achieved,
The new, injectable nano-network is composed of a mixture containing nanoparticles with a solid core of insulin, modified dextran and glucose oxidase enzymes. When the enzymes are exposed to high glucose levels they effectively convert glucose into gluconic acid, which breaks down the modified dextran and releases the insulin. The insulin then brings the glucose levels under control. The gluconic acid and dextran are fully biocompatible and dissolve in the body.
Each of these nanoparticle cores is given either a positively charged or negatively charged biocompatible coating. The positively charged coatings are made of chitosan (a material normally found in shrimp shells), while the negatively charged coatings are made of alginate (a material normally found in seaweed).
When the solution of coated nanoparticles is mixed together, the positively and negatively charged coatings are attracted to each other to form a “nano-network.” Once injected into the subcutaneous layer of the skin, the nano-network holds the nanoparticles together and prevents them from dispersing throughout the body. Both the nano-network and the coatings are porous, allowing blood – and blood sugar – to reach the nanoparticle cores.
“This technology effectively creates a ‘closed-loop’ system that mimics the activity of the pancreas in a healthy patient, releasing insulin in response to glucose level changes,” Gu says. “This has the potential to improve the health and quality of life of diabetes patients.”
For anyone who’s interested in researching further, heres’ a citation for and a link to the paper,
The paper is behind a paywall. Meanwhile, there are discussions about moving these injectable nano-networks into human clinical trials. As Nie notes, Iron Man 3 hints at new medical technologies which will be achievable in the next 10 or so years, although we may have to wait 100 to 150 years for Extremis armor.
1920, the year mathematician Srinivasa Ramanujan died, is also the year he left behind mathematical formulas that may help unlock the secrets of black holes (from the Dec. 11, 2012 posting by Carol Clark for Emory University’s e-science commons blog),
“No one was talking about black holes back in the 1920s when Ramanujan first came up with mock modular forms, and yet, his work may unlock secrets about them,” Ono [Emory University mathematician Ken Ono] says.
Expansion of modular forms is one of the fundamental tools for computing the entropy of a modular black hole. Some black holes, however, are not modular, but the new formula based on Ramanujan’s vision may allow physicists to compute their entropy as though they were.
Ramanujan was on his death bed (at the age of 32) when he devised his last formulas (from the Clark posting),
Accessed from http://esciencecommons.blogspot.ca/2012/12/math-formula-gives-new-glimpse-into.html
… A devout Hindu, Ramanujan said that his findings were divine, revealed to him in dreams by the goddess Namagiri.
While on his death-bed in 1920, Ramanujan wrote a letter to his mentor, English mathematician G. H. Hardy. The letter described several new functions that behaved differently from known theta functions, or modular forms, and yet closely mimicked them. Ramanujan conjectured that his mock modular forms corresponded to the ordinary modular forms earlier identified by Carl Jacobi, and that both would wind up with similar outputs for roots of 1.
No one at the time understood what Ramanujan was talking about. “It wasn’t until 2002, through the work of Sander Zwegers, that we had a description of the functions that Ramanujan was writing about in 1920,” Ono says.
This year (2012) a number of special events have been held to commemorate Ramanujan’s accomplishments (Note: I have removed links), from the Clark posting,
December 22  marks the 125th anniversary of the birth of Srinivasa Ramanujan, an Indian mathematician renowned for somehow intuiting extraordinary numerical patterns and connections without the use of proofs or modern mathematical tools. ..
“I wanted to do something special, in the spirit of Ramanujan, to mark the anniversary,” says Emory mathematician Ken Ono. “It’s fascinating to me to explore his writings and imagine how his brain may have worked. It’s like being a mathematical anthropologist.”
Ono, a number theorist whose work has previously uncovered hidden meanings in the notebooks of Ramanujan, set to work on the 125th-anniversary project with two colleagues and former students: Amanda Folsom, from Yale, and Rob Rhoades, from Stanford.
The result is a formula for mock modular forms that may prove useful to physicists who study black holes. The work, which Ono recently presented at the Ramanujan 125 conference at the University of Florida, also solves one of the greatest puzzles left behind by the enigmatic Indian genius.
Here’s a trailer for the forthcoming movie (a docu-drama) about Ramanujan, from the Clark posting,
Here’s a description of Ramanujan from Wikipedia, which gives some insight into the nature of his genius (Note: I have removed links and a footnote),
Srinivasa Ramanujan FRS (…) (22 December 1887 – 26 April 1920) was an Indian mathematician and autodidact who, with almost no formal training in pure mathematics, made extraordinary contributions to mathematical analysis, number theory, infinite series, and continued fractions. Living in India with no access to the larger mathematical community, which was centered in Europe at the time, Ramanujan developed his own mathematical research in isolation. As a result, he sometimes rediscovered known theorems in addition to producing new work. Ramanujan was said to be a natural genius by the English mathematician G.H. Hardy, in the same league as mathematicians like Euler and Gauss.
There is a little more to Ono’s latest work concerning Ramanujan’s deathbed math functions (from the Clark posting),
After coming up with the formula for computing a mock modular form, Ono wanted to put some icing on the cake for the 125th-anniversary celebration. He and Emory graduate students Michael Griffin and Larry Rolen revisited the paragraph in Ramanujan’s last letter that gave a vague description for how he arrived at the functions. That one paragraph has inspired hundreds of papers by mathematicians, who have pondered its hidden meaning for eight decades.
“So much of what Ramanujan offers comes from mysterious words and strange formulas that seem to defy mathematical sense,” Ono says. “Although we had a definition from 2002 for Ramanujan’s functions, it was still unclear how it related to Ramanujan’s awkward and imprecise definition.”
Ono and his students finally saw the meaning behind the puzzling paragraph, and a way to link it to the modern definition. “We developed a theorem that shows that the bizarre methodology he used to construct his examples is correct,” Ono says. “For the first time, we can prove that the exotic functions that Ramanujan conjured in his death-bed letter behave exactly as he said they would, in every case.”
Ono is now on a mathematicians’ tour in India (from the Clark posting),
Ono will spend much of December in India, taking overnight trains to Mysore, Bangalore, Chennai and New Dehli, as part of a group of distinguished mathematicians giving talks about Ramanujan in the lead-up to the anniversary date.
“Ramanujan is a hero in India so it’s kind of like a math rock tour,” Ono says, adding, “I’m his biggest fan. My professional life is inescapably intertwined with Ramanujan. Many of the mathematical objects that I think about so profoundly were anticipated by him. I’m so glad that he existed.”
Between this and the series developed by Alex Bellos about mathematics in Japan (my Oct. 17, 2012 posting), it seems that attention is turning eastward where the study and development of mathematics is concerned. H/T to EurekAlert’s Dec. 17, 2012 news release and do read Clark’s article if you want more information about Ono and Ramanujan.
Glass isn’t transparent (at the molecular scale) as it’s cooling and scientists have been curious about this transition from liquid to glass state. According to an Oct. 15, 2012 posting by Carol Clark for Emory University’s eScienceCommons, a team from Emory University (and New York University) has cracked this mystery. First, here’s more about the mystery (from Clark’s article)
Scientists fully understand the process of water turning to ice. As the temperature cools, the movement of the water molecules slows. At 32 F, the molecules lock into crystal lattices, solidifying into ice. In contrast, the molecules of glasses do not crystallize.The movement of the glass molecules slows as the temperature cools, but they never lock into crystal patterns. Instead, they jumble up and gradually become glassier, or more viscous. No one understands exactly why.
The phenomenon leaves physicists to ponder the molecular question of whether glass is a solid, or merely an extremely slow-moving liquid.
This purely technical physics question has stoked a popular misconception: That the glass in the windowpanes of some centuries-old buildings is thicker at the bottom because the glass flowed downward over time.
“The real reason the bottom is thicker is because they hadn’t yet learned how to make perfectly flat panes of glass,” Weeks says [Emory physicist Eric Weeks]. “For practical purposes, glass is a solid and it will not flow, even over centuries. But there is a kernel of truth in this urban legend: Glasses are different than other solid materials.”
Speaking more technically about the transition,
“Cooling a glass from a liquid into a highly viscous state fundamentally changes the nature of particle diffusion,” says Emory physicist Eric Weeks, whose lab conducted the research. “We have provided the first direct observation of how the particles move and tumble through space during this transition, a key piece to a major puzzle in condensed matter physics.”
Weeks specializes in “soft condensed materials,” substances that cannot be pinned down on the molecular level as a solid or liquid, including everyday substances such as toothpaste, peanut butter, shaving cream, plastic and glass.
The scientists have prepared a video animation of what they believing is occurring as glass cools (no sound),
Here’s what the movie depicts (from the Clark article),
The movie and data from the experiment provide the first clear picture of the particle dynamics for glass formation. As the liquid grows slightly more viscous, both rotational and directional particle motion slows. The amount of rotation and the directional movements of the particles remain correlated.
“Normally, these two types of motion are highly coupled,” Weeks says. “This remains true until the system reaches a viscosity on the verge of being glass. Then the rotation and directional movements become decoupled: The rotation starts slowing down more.”
He uses a gridlocked parking lot as an analogy for how the particles are behaving. “You can’t turn your car around, because it’s not a sphere shape and you would bump into your neighbors. You have to wait until a car in front of you moves, and then you can drive a bit in that direction. This is directional movement, and if you can make a bunch of these, you may eventually be able to turn your car. But turning in a crowded parking lot is still much harder than moving in a straight line.”
There’s more about the work and team in Clark’s article. H/T to the Oct. 16, 2012 news item on Nanowerk for alerting me to this work. You can find the article the researchers have written at the Proceedings of the National Academy of Sciences (PNAS),