Category Archives: human enhancement

Neural and technological inequalities

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

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

The ethics of ‘neural inequality’

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

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

Opening new pathways to thought through bionics

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

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

The innovation of your human body

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

Democratizing tech’s edges

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

Earlier technology that changed our thinking and thoughts

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

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

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

Who’s talking about technology and our thinking?

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

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

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

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

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

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

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

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

Human-machine interfaces and ultra-small nanoprobes

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Ethics of germline editing special CRISPR journal issue

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

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

Highlights from this Issue:

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

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

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

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

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

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

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

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

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

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

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

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

Detecting off-target effects of CRISPR gene-editing

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

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

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

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

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

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

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

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

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

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

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

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

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

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

###

About the Study

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

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

About the Gladstone Institute

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

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

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

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

This paper is behind a paywall.

Money

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

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

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

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

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

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

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

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

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

Anand Giridharadas‏Verified account @AnandWrites



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

7:34 PM – 8 Jul 2019

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

AstraZeneca

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

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

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

Controversies

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

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

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

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

Innovative Genomics Institute (IGI)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Gladstone Institutes

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Final comments

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

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

Needle-free tattoos, smart and otherwise

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

Why this event?

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

Open Event

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


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

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

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

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

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

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

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

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

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

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

Fast fluid jet

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

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

Skin treatment

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

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

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

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

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

This paper appears to be open access.

Cyborgs based on melanin circuits

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

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

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

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

This is a rather dreamy image to illustrate the point,

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This paper is open access.

Ankle exoskeletons good for people who need to do a lot of walking or running on the job

For people who need a little extra ankle support, this might be useful in the, hopefully, not too distant future.

The new ankle exoskeleton design integrates into the shoe and under clothing. Submitted photo. Courtesy of Vanderbilt University Credit: Matthew Yandell

A March 22, 2019 news item on ScienceDaily announces this latest research,

A new lightweight, low-profile and inexpensive ankle exoskeleton could be widely used among elderly people, those with impaired lower-leg muscle strength and workers whose jobs require substantial walking or running.

Developed by Vanderbilt mechanical engineers, the device is believed to be the first ankle exoskeleton that could be worn under clothes without restricting motion. It does not require additional components such as batteries or actuators carried on the back or waist.

A March 21, 2019 Venderbilt University news release (also on EurekAlert but published March 22, 2019), offers more detail,

The study, published online by IEEE Transactions on Neural Systems & Rehabilitation Engineering, builds on a successful and widely cited ankle exoskeleton concept from other researchers in 2015.

“We’ve shown how an unpowered ankle exoskeleton could be redesigned to fit under clothing and inside/under shoes so it more seamlessly integrates into daily life,” said Matt Yandell, a mechanical engineering Ph.D. student and lead author of the study.

In a significant design advancement, the team invented an unpowered friction clutch mechanism that fits under the foot or shoe and is no thicker than a typical shoe insole. The complete device, which includes a soft shank sleeve and assistive spring, weighs just over one pound.

The unpowered ankle exoskeleton costs less than $100 to fabricate, without factoring in optimized design for manufacturing and economies of scale.

“Our design is lightweight, low profile, quiet, uses no motor or batteries, it is low cost to manufacture, and naturally adapts to different walking speeds to assist the ankle muscles,” said Karl Zelik, assistant professor of mechanical engineering and senior author on the study.

Zelik will be presenting this work next week at the Wearable Robotics Association Conference in Phoenix, Arizona [March 26-28, 2019].

The potential applications are broad, from helping aging people stay active to assisting recreational walkers, hikers or runners, he said.

“It could also help reduce fatigue in occupations that involve lots of walking, such as postal and warehouse workers, and soldiers in the field,” Zelik said.

Joshua Tacca, BE’18, also is a co-author. He is now a graduate student in the Integrative Physiology Department at the University of Colorado-Boulder. Several other Vanderbilt undergraduate engineering students also contributed to the device design and pilot testing.

I wonder if this device requires a particular kind of shoe. In any event, here’s a link to and a citation for the study,

Design of a Low Profile, Unpowered Ankle Exoskeleton That Fits Under Clothes: Overcoming Practical Barriers to Widespread Societal Adoption by Matthew B. Yandell, Joshua R. Tacca, and Karl E. Zelik. IEEE Transactions on Neural Systems & Rehabilitation Engineering 2019; 1 DOI: 10.1109/TNSRE.2019.2904924 Date of Publication: 14 March 2019 (early access)

This study appears to be behind a paywall

Iron oxide nanoparticles for artificial skin with super powers

A January 28, 2019 news item on ScienceDaily describes the possibilities for a skin replacement material,

A new type of sensor could lead to artificial skin that someday helps burn victims ‘feel’ and safeguards the rest of us, University of Connecticut researchers suggest in a paper in Advanced Materials.

Our skin’s ability to perceive pressure, heat, cold, and vibration is a critical safety function that most people take for granted. But burn victims, those with prosthetic limbs, and others who have lost skin sensitivity for one reason or another, can’t take it for granted, and often injure themselves unintentionally.

Chemists Islam Mosa from UConn [University of Connecticut], and James Rusling from UConn and UConn Health, along with University of Toronto engineer Abdelsalam Ahmed, wanted to create a sensor that can mimic the sensing properties of skin. Such a sensor would need to be able to detect pressure, temperature, and vibration. But perhaps it could do other things too, the researchers thought.

“It would be very cool if it had abilities human skin does not; for example, the ability to detect magnetic fields, sound waves, and abnormal behaviors,” said Mosa.

A January 22, 2019 UConn news release (also on EurekAlert but dated January 28, 2019), which originated the news item, give more detail about the work,

Mosa and his colleagues created such a sensor with a silicone tube wrapped in a copper wire and filled with a special fluid made of tiny particles of iron oxide just one billionth of a meter long, called nanoparticles. The nanoparticles rub around the inside of the silicone tube and create an electric current. The copper wire surrounding the silicone tube picks up the current as a signal. When this tube is bumped by something experiencing pressure, the nanoparticles move and the electric signal changes. Sound waves also create waves in the nanoparticle fluid, and the electric signal changes in a different way than when the tube is bumped.

The researchers found that magnetic fields alter the signal too, in a way distinct from pressure or sound waves. Even a person moving around while carrying the sensor changes the electrical current, and the team found they could distinguish between the electrical signals caused by walking, running, jumping, and swimming.

Metal skin might sound like a superhero power, but this skin wouldn’t make the wearer Colossus from the X-men. Rather, Mosa and his colleagues hope it could help burn victims “feel” again, and perhaps act as an early warning for workers exposed to dangerously high magnetic fields. Because the rubber exterior is completely sealed and waterproof, it could also serve as a wearable monitor to alert parents if their child fell into deep water in a pool, for example.

“The inspiration was to make something durable that would last for a very long time, and could detect multiple hazards,” Mosa says. The team has yet to test the sensor for its response to heat and cold, but they suspect it will work for those as well. The next step is to make the sensor in a flat configuration, more like skin, and see if it still works.

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

An Ultra‐Shapeable, Smart Sensing Platform Based on a Multimodal Ferrofluid‐Infused Surface by Abdelsalam Ahmed, Islam Hassan, Islam M. Mosa, Esraa Elsanadidy, Mohamed Sharafeldin, James F. Rusling, Shenqiang Ren. Advanced Materials DOI: https://doi.org/10.1002/adma.201807201 First published: 28 January 2019

This paper is behind a paywall.

Greater mortality for the CRISPR twins Lulu and Nana?

Every time I think this CRISPR (clustered regularly interspaced short palindromic repeats) story is winding down, something new happens. The latest (I think) is in a June 3, 2019 news item on ScienceDaily,

A genetic mutation that a Chinese scientist attempted to create in twin babies born last year, ostensibly to help them fend off HIV infection, is also associated with a 21% increase in mortality in later life, according to an analysis by University of California, Berkeley, scientists.

The researchers scanned more than 400,000 genomes and associated health records contained in a British database, UK Biobank, and found that people who had two mutated copies of the gene had a significantly higher death rate between ages 41 and 78 than those with one or no copies.

Sarah Zhang’s June 3, 2019 article for The Atlantic provides an overview of the situation before exploring the current controversy,

In the 1990s, virologists in New York learned of a genetic mutation that would become one of the most famous ever discovered. They found it in a man who could not be infected with HIV. He turned out to be missing just 32 letters in a gene called CCR5, and remarkably, it was enough to make him resistant to the virus killing so many others. About 1 percent of people of European descent carry two copies of this mutation, now known as CCR5-Δ32.

In 2018, a Chinese scientist named He Jiankui made the mutation infamous when he attempted to use CRISPR to edit CCR5-Δ32 (pronounced “CCR5-delta-32”) into human embryos. He chose this mutation, he said, because the babies’ father was HIV-positive, and he wanted to make the resulting twin girls resistant to the virus. CCR5-Δ32 is also, after all, one of the most studied mutations.

He’s work immediately provoked outrage among scientists, who knew enough to know how much they did not know about the risks of altering CCR5. And now a new study suggests that CCR5-Δ32 is indeed harmful overall.

The girls’ CCR5 genes were altered, according to data He presented, but they do not exactly match the 32-letter deletion; it’s unclear whether either of them is actually resistant to HIV. Even if they were unable to get HIV, a body of research already suggested that CCR5-Δ32 made people more vulnerable to the flu and West Nile virus. A “good” mutation in the context of HIV can be “bad” in another context. No one knew, exactly, the net effect of a CCR5-Δ32 mutation.

For some reason, Zhang makes no mention of the possibly enhanced cognitive abilities that the twins may have as a consequence of the gene editing assuming that He Jiankui successfully edited the genes. (To my knowledge, the results and data have not been released for review by colleagues.)

Regardless, Zhang’s article provides a handy overview and update.

For anyone who’s interested in more detail about this latest research into mortality and CCR5, there’s a June 3, 2019 University of California at Berkeley news release (also on EurekAlert) by Robert Sanders, which also originated the ScienceDaily news item, details the latest research,

Previous studies have associated two mutated copies of the gene, CCR5, with a fourfold increase in the death rate after influenza infection, and the higher overall mortality rate may reflect this greater susceptibility to death from the flu. But the researchers say there could be any number of explanations, since the protein that CCR5 codes for, and which no longer works in those having the mutation in both copies of the gene, is involved in many body functions.

“Beyond the many ethical issues involved with the CRISPR babies, the fact is that, right now, with current knowledge, it is still very dangerous to try to introduce mutations without knowing the full effect of what those mutations do,” said Rasmus Nielsen, a UC Berkeley professor of integrative biology. “In this case, it is probably not a mutation that most people would want to have. You are actually, on average, worse off having it.”

“Because one gene could affect multiple traits, and because, depending on the environment, the effects of a mutation could be quite different, I think there can be many uncertainties and unknown effects in any germline editing,” said postdoctoral fellow Xinzhu “April” Wei.
Wei is first author and Nielsen is senior author of a paper describing the research that will appear online on Monday, June 3, in the journal Nature Medicine.

Mutation prevents HIV infection

The gene CCR5 codes for a protein that, among other things, sits on the surface of immune cells and helps some strains of HIV, including the most common ones, to enter and infect them. Jiankui He, the Chinese scientist who last November shocked the world by announcing he had experimented with CCR5 on at least two babies, said he wanted to introduce a mutation in the gene that would prevent this. Naturally-occurring mutations that disable the protein are rare in Asians, but a mutation found in about 11% of Northern Europeans protects them against HIV infection.

The genetic mutation, ∆32 (Delta 32), refers to a missing 32-base-pair segment in the CCR5 gene. This mutation interferes with the localization on the cell surface of the protein for which CCR5 codes, thwarting HIV binding and infection. He was unable to duplicate the natural mutation, but appears to have generated a similar deletion that would also inactivate the protein. One of the twin babies reportedly had one copy of CCR5 modified by CRISPR-Cas9 gene editing, while the other baby had both copies edited.

But inactivating a protein found in all humans and most animals is likely to have negative effects, Nielsen said, especially when done to both copies of the gene — a so-called homozygous mutation

“Here is a functional protein that we know has an effect in the organism, and it is well-conserved among many different species, so it is likely that a mutation that destroys the protein is, on average, not good for you,” he said. “Otherwise, evolutionary mechanisms would have destroyed that protein a long time ago.”

After He’s experiment became public, Nielsen and Wei, who study current genetic variation to understand the origin of human, animal and plant traits, decided to investigate the effect of the CCR5-∆32 mutation using data from UK Biobank. The database houses genomic information on a half million U.K. citizens that is linked to their medical records. The genomic information is much like that acquired by Ancestry.com and 23andMe: details on nearly a million individual variations in the genetic sequence, so-called single nucleotide polymorphisms (SNPs).

Two independent measures indicated a higher mortality rate for those with two mutated genes. Fewer people than expected with two mutations enrolled in the database, indicating that they had died at a higher rate than the general population. And fewer than expected survived from ages 40 to 78.

“Both the proportions before enrollment and the survivorship after enrollment tell the same story, which is that you have lower survivability or higher mortality if you have two copies of the mutation,” Nielsen said. “There is simply a deficiency of individuals with two copies.”

Because the ∆32 mutation is relatively common in Northern Europeans, it must have been favored by natural selection at some point, Nielsen said, though probably not to protect against HIV, since the virus has circulated among humans only since the 1980s.

Wei said that some evidence links the mutation to increased survival after stroke and protection against smallpox and flaviviruses, a group that includes the dengue, Zika and West Nile viruses.

Despite these possible benefits, the potential unintended effects of creating genetic mutations, in both adult somatic cells and in embryonic, germline cells, argue for caution, the researchers said.

“I think there are a lot of things that are unknown at the current stage about genes’ functions,” Wei said. “The CRISPR technology is far too dangerous to use right now for germline editing.”

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

CCR5-∆32 is deleterious in the homozygous state in humans by Xinzhu Wei & Rasmus Nielsen. Nature Medicine (2019) DOI: https://doi.org/10.1038/s41591-019-0459-6 Published 03 June 2019

This paper is behind a paywall.

For those who have an insatiable appetite for detail, there’s my November 28, 2018 posting which covers what happened when the CRISPR twins, Lulu and Nana, was first announced, along with a few updates to January 23, 2019. The May 17, 2019 posting covers the news of possible cognitive advantages for the CCR5-Δ32 gene-edited twins and explores some of the social implications.

Two approaches to memristors

Within one day of each other in October 2018, two different teams working on memristors with applications to neuroprosthetics and neuromorphic computing (brainlike computing) announced their results.

Russian team

An October 15, 2018 (?) Lobachevsky University press release (also published on October 15, 2018 on EurekAlert) describes a new approach to memristors,

Biological neurons are coupled unidirectionally through a special junction called a synapse. An electrical signal is transmitted along a neuron after some biochemical reactions initiate a chemical release to activate an adjacent neuron. These junctions are crucial for cognitive functions, such as perception, learning and memory.

A group of researchers from Lobachevsky University in Nizhny Novgorod investigates the dynamics of an individual memristive device when it receives a neuron-like signal as well as the dynamics of a network of analog electronic neurons connected by means of a memristive device. According to Svetlana Gerasimova, junior researcher at the Physics and Technology Research Institute and at the Neurotechnology Department of Lobachevsky University, this system simulates the interaction between synaptically coupled brain neurons while the memristive device imitates a neuron axon.

A memristive device is a physical model of Chua’s [Dr. Leon Chua, University of California at Berkeley; see my May 9, 2008 posting for a brief description Dr. Chua’s theory] memristor, which is an electric circuit element capable of changing its resistance depending on the electric signal received at the input. The device based on a Au/ZrO2(Y)/TiN/Ti structure demonstrates reproducible bipolar switching between the low and high resistance states. Resistive switching is determined by the oxidation and reduction of segments of conducting channels (filaments) in the oxide film when voltage with different polarity is applied to it. In the context of the present work, the ability of a memristive device to change conductivity under the action of pulsed signals makes it an almost ideal electronic analog of a synapse.

Lobachevsky University scientists and engineers supported by the Russian Science Foundation (project No.16-19-00144) have experimentally implemented and theoretically described the synaptic connection of neuron-like generators using the memristive interface and investigated the characteristics of this connection.

“Each neuron is implemented in the form of a pulse signal generator based on the FitzHugh-Nagumo model. This model provides a qualitative description of the main neurons’ characteristics: the presence of the excitation threshold, the presence of excitable and self-oscillatory regimes with the possibility of a changeover. At the initial time moment, the master generator is in the self-oscillatory mode, the slave generator is in the excitable mode, and the memristive device is used as a synapse. The signal from the master generator is conveyed to the input of the memristive device, the signal from the output of the memristive device is transmitted to the input of the slave generator via the loading resistance. When the memristive device switches from a high resistance to a low resistance state, the connection between the two neuron-like generators is established. The master generator goes into the oscillatory mode and the signals of the generators are synchronized. Different signal modulation mode synchronizations were demonstrated for the Au/ZrO2(Y)/TiN/Ti memristive device,” – says Svetlana Gerasimova.

UNN researchers believe that the next important stage in the development of neuromorphic systems based on memristive devices is to apply such systems in neuroprosthetics. Memristive systems will provide a highly efficient imitation of synaptic connection due to the stochastic nature of the memristive phenomenon and can be used to increase the flexibility of the connections for neuroprosthetic purposes. Lobachevsky University scientists have vast experience in the development of neurohybrid systems. In particular, a series of experiments was performed with the aim of connecting the FitzHugh-Nagumo oscillator with a biological object, a rat brain hippocampal slice. The signal from the electronic neuron generator was transmitted through the optic fiber communication channel to the bipolar electrode which stimulated Schaffer collaterals (axons of pyramidal neurons in the CA3 field) in the hippocampal slices. “We are going to combine our efforts in the design of artificial neuromorphic systems and our experience of working with living cells to improve flexibility of prosthetics,” concludes S. Gerasimova.

The results of this research were presented at the 38th International Conference on Nonlinear Dynamics (Dynamics Days Europe) at Loughborough University (Great Britain).

This diagram illustrates an aspect of the work,

Caption: Schematic of electronic neurons coupling via a memristive device. Credit: Lobachevsky University

US team

The American Institute of Physics (AIP) announced the publication of a ‘memristor paper’ by a team from the University of Southern California (USC) in an October 16, 2018 news item on phys.org,

Just like their biological counterparts, hardware that mimics the neural circuitry of the brain requires building blocks that can adjust how they synapse, with some connections strengthening at the expense of others. One such approach, called memristors, uses current resistance to store this information. New work looks to overcome reliability issues in these devices by scaling memristors to the atomic level.

An October 16, 2018 AIP news release (also on EurekAlert), which originated the news item, delves further into the particulars of this particular piece of memristor research,

A group of researchers demonstrated a new type of compound synapse that can achieve synaptic weight programming and conduct vector-matrix multiplication with significant advances over the current state of the art. Publishing its work in the Journal of Applied Physics, from AIP Publishing, the group’s compound synapse is constructed with atomically thin boron nitride memristors running in parallel to ensure efficiency and accuracy.

The article appears in a special topic section of the journal devoted to “New Physics and Materials for Neuromorphic Computation,” which highlights new developments in physical and materials science research that hold promise for developing the very large-scale, integrated “neuromorphic” systems of tomorrow that will carry computation beyond the limitations of current semiconductors today.

“There’s a lot of interest in using new types of materials for memristors,” said Ivan Sanchez Esqueda, an author on the paper. “What we’re showing is that filamentary devices can work well for neuromorphic computing applications, when constructed in new clever ways.”

Current memristor technology suffers from a wide variation in how signals are stored and read across devices, both for different types of memristors as well as different runs of the same memristor. To overcome this, the researchers ran several memristors in parallel. The combined output can achieve accuracies up to five times those of conventional devices, an advantage that compounds as devices become more complex.

The choice to go to the subnanometer level, Sanchez said, was born out of an interest to keep all of these parallel memristors energy-efficient. An array of the group’s memristors were found to be 10,000 times more energy-efficient than memristors currently available.

“It turns out if you start to increase the number of devices in parallel, you can see large benefits in accuracy while still conserving power,” Sanchez said. Sanchez said the team next looks to further showcase the potential of the compound synapses by demonstrating their use completing increasingly complex tasks, such as image and pattern recognition.

Here’s an image illustrating the parallel artificial synapses,

Caption: Hardware that mimics the neural circuitry of the brain requires building blocks that can adjust how they synapse. One such approach, called memristors, uses current resistance to store this information. New work looks to overcome reliability issues in these devices by scaling memristors to the atomic level. Researchers demonstrated a new type of compound synapse that can achieve synaptic weight programming and conduct vector-matrix multiplication with significant advances over the current state of the art. They discuss their work in this week’s Journal of Applied Physics. This image shows a conceptual schematic of the 3D implementation of compound synapses constructed with boron nitride oxide (BNOx) binary memristors, and the crossbar array with compound BNOx synapses for neuromorphic computing applications. Credit: Ivan Sanchez Esqueda

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

Efficient learning and crossbar operations with atomically-thin 2-D material compound synapses by Ivan Sanchez Esqueda, Huan Zhao and Han Wang. The article will appear in the Journal of Applied Physics Oct. 16, 2018 (DOI: 10.1063/1.5042468).

This paper is behind a paywall.

*Title corrected from ‘Two approaches to memristors featuring’ to ‘Two approaches to memristors’ on May 31, 2019 at 1455 hours PDT.