Tag Archives: University of California at San Francisco

Restoring words with a neuroprosthesis

There seems to have been an update to the script for the voiceover. You’ll find it at the 1 min. 30 secs. mark (spoken: “with up to 93% accuracy at 18 words per minute`’ vs. written “with median 74% accuracy at 15 words per minute)".

A July 14, 2021 news item on ScienceDaily announces the latest work on a neuroprosthetic from the University of California at San Francisco (UCSF),

Researchers at UC San Francisco have successfully developed a “speech neuroprosthesis” that has enabled a man with severe paralysis to communicate in sentences, translating signals from his brain to the vocal tract directly into words that appear as text on a screen.
The achievement, which was developed in collaboration with the first participant of a clinical research trial, builds on more than a decade of effort by UCSF neurosurgeon Edward Chang, MD, to develop a technology that allows people with paralysis to communicate even if they are unable to speak on their own. The study appears July 15 [2021] in the New England Journal of Medicine.

A July 14, 2021 UCSF news release (also on EurekAlert), which originated the news item, delves further into the topic,

“To our knowledge, this is the first successful demonstration of direct decoding of full words from the brain activity of someone who is paralyzed and cannot speak,” said Chang, the Joan and Sanford Weill Chair of Neurological Surgery at UCSF, Jeanne Robertson Distinguished Professor, and senior author on the study. “It shows strong promise to restore communication by tapping into the brain’s natural speech machinery.”
Each year, thousands of people lose the ability to speak due to stroke, accident, or disease. With further development, the approach described in this study could one day enable these people to fully communicate.
Translating Brain Signals into Speech
Previously, work in the field of communication neuroprosthetics has focused on restoring communication through spelling-based approaches to type out letters one-by-one in text. Chang’s study differs from these efforts in a critical way: his team is translating signals intended to control muscles of the vocal system for speaking words, rather than signals to move the arm or hand to enable typing. Chang said this approach taps into the natural and fluid aspects of speech and promises more rapid and organic communication.
“With speech, we normally communicate information at a very high rate, up to 150 or 200 words per minute,” he said, noting that spelling-based approaches using typing, writing, and controlling a cursor are considerably slower and more laborious. “Going straight to words, as we’re doing here, has great advantages because it’s closer to how we normally speak.”
Over the past decade, Chang’s progress toward this goal was facilitated by patients at the UCSF Epilepsy Center who were undergoing neurosurgery to pinpoint the origins of their seizures using electrode arrays placed on the surface of their brains. These patients, all of whom had normal speech, volunteered to have their brain recordings analyzed for speech-related activity. Early success with these patient volunteers paved the way for the current trial in people with paralysis.
Previously, Chang and colleagues in the UCSF Weill Institute for Neurosciences mapped the cortical activity patterns associated with vocal tract movements that produce each consonant and vowel. To translate those findings into speech recognition of full words, David Moses, PhD, a postdoctoral engineer in the Chang lab and lead author of the new study, developed new methods for real-time decoding of those patterns, as well as incorporating statistical language models to improve accuracy.
But their success in decoding speech in participants who were able to speak didn’t guarantee that the technology would work in a person whose vocal tract is paralyzed. “Our models needed to learn the mapping between complex brain activity patterns and intended speech,” said Moses. “That poses a major challenge when the participant can’t speak.”
In addition, the team didn’t know whether brain signals controlling the vocal tract would still be intact for people who haven’t been able to move their vocal muscles for many years. “The best way to find out whether this could work was to try it,” said Moses.
The First 50 Words
To investigate the potential of this technology in patients with paralysis, Chang partnered with colleague Karunesh Ganguly, MD, PhD, an associate professor of neurology, to launch a study known as “BRAVO” (Brain-Computer Interface Restoration of Arm and Voice). The first participant in the trial is a man in his late 30s who suffered a devastating brainstem stroke more than 15 years ago that severely damaged the connection between his brain and his vocal tract and limbs. Since his injury, he has had extremely limited head, neck, and limb movements, and communicates by using a pointer attached to a baseball cap to poke letters on a screen.
The participant, who asked to be referred to as BRAVO1, worked with the researchers to create a 50-word vocabulary that Chang’s team could recognize from brain activity using advanced computer algorithms. The vocabulary – which includes words such as “water,” “family,” and “good” – was sufficient to create hundreds of sentences expressing concepts applicable to BRAVO1’s daily life.
For the study, Chang surgically implanted a high-density electrode array over BRAVO1’s speech motor cortex. After the participant’s full recovery, his team recorded 22 hours of neural activity in this brain region over 48 sessions and several months. In each session, BRAVO1 attempted to say each of the 50 vocabulary words many times while the electrodes recorded brain signals from his speech cortex.
Translating Attempted Speech into Text
To translate the patterns of recorded neural activity into specific intended words, Moses’s two co-lead authors, Sean Metzger and Jessie Liu, both bioengineering graduate students in the Chang Lab, used custom neural network models, which are forms of artificial intelligence. When the participant attempted to speak, these networks distinguished subtle patterns in brain activity to detect speech attempts and identify which words he was trying to say.
To test their approach, the team first presented BRAVO1 with short sentences constructed from the 50 vocabulary words and asked him to try saying them several times. As he made his attempts, the words were decoded from his brain activity, one by one, on a screen.
Then the team switched to prompting him with questions such as “How are you today?” and “Would you like some water?” As before, BRAVO1’s attempted speech appeared on the screen. “I am very good,” and “No, I am not thirsty.”
Chang and Moses found that the system was able to decode words from brain activity at rate of up to 18 words per minute with up to 93 percent accuracy (75 percent median). Contributing to the success was a language model Moses applied that implemented an “auto-correct” function, similar to what is used by consumer texting and speech recognition software.
Moses characterized the early trial results as a proof of principle. “We were thrilled to see the accurate decoding of a variety of meaningful sentences,” he said. “We’ve shown that it is actually possible to facilitate communication in this way and that it has potential for use in conversational settings.”
Looking forward, Chang and Moses said they will expand the trial to include more participants affected by severe paralysis and communication deficits. The team is currently working to increase the number of words in the available vocabulary, as well as improve the rate of speech.
Both said that while the study focused on a single participant and a limited vocabulary, those limitations don’t diminish the accomplishment. “This is an important technological milestone for a person who cannot communicate naturally,” said Moses, “and it demonstrates the potential for this approach to give a voice to people with severe paralysis and speech loss.”
… all of UCSF. Funding sources [emphasis mine] included National Institutes of Health (U01 NS098971-01), philanthropy, and a sponsored research agreement with Facebook Reality Labs (FRL), [emphasis mine] which completed in early 2021.
UCSF researchers conducted all clinical trial design, execution, data analysis and reporting. Research participant data were collected solely by UCSF, are held confidentially, and are not shared with third parties. FRL provided high-level feedback and machine learning advice.

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

Neuroprosthesis for Decoding Speech in a Paralyzed Person with Anarthria by David A. Moses, Ph.D., Sean L. Metzger, M.S., Jessie R. Liu, B.S., Gopala K. Anumanchipalli, Ph.D., Joseph G. Makin, Ph.D., Pengfei F. Sun, Ph.D., Josh Chartier, Ph.D., Maximilian E. Dougherty, B.A., Patricia M. Liu, M.A., Gary M. Abrams, M.D., Adelyn Tu-Chan, D.O., Karunesh Ganguly, M.D., Ph.D., and Edward F. Chang, M.D. N Engl J Med 2021; 385:217-227 DOI: 10.1056/NEJMoa2027540 Published July 15, 2021

This paper is mostly behind a paywall but you do have this option: “Create your account to get 2 free subscriber-only articles each month.”

*Sept. 4, 2023 I have made a few minor corrections (a) removed an extra space (b) removed an extra ‘a’.

Revival of dead pig brains raises moral questions about life and death

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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.
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… “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.
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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

This paper is behind a paywall.

Two neuroethicists had this to say (link to their commentary in Nature follows) as per an April 71, 2019 news release from Case Western Reserve University (also on EurekAlert), Note: Links have been removed,

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,

Pig experiment challenges assumptions around brain damage in people by Stuart Youngner and Insoo Hyun. Nature 568, 302-304 (2019) DOI: 10.1038/d41586-019-01169-8 April 17, 2019

This paper is open access.

I was hoping to find out more about BrainEx, but this April 17, 2019 US National Institute of Mental Health news release is all I’ve been able to find in my admittedly brief online search. The news release offers more celebration than technical detail.

Quick comment

Interestingly, there hasn’t been much of a furor over this work. Not yet.

Detecting off-target effects of CRISPR gene-editing

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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.
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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.”
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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]
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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.
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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).
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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]
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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
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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]
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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.
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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]
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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]
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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.

CRISPR-Cas12a as a new diagnostic tool

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Similar to Cas9, Cas12a is has an added feature as noted in this February 15, 2018 news item on ScienceDaily,

Utilizing an unsuspected activity of the CRISPR-Cas12a protein, researchers created a simple diagnostic system called DETECTR to analyze cells, blood, saliva, urine and stool to detect genetic mutations, cancer and antibiotic resistance and also diagnose bacterial and viral infections. The scientists discovered that when Cas12a binds its double-stranded DNA target, it indiscriminately chews up all single-stranded DNA. They then created reporter molecules attached to single-stranded DNA to signal when Cas12a finds its target.

A February 15, 2018 University of California at Berkeley (UC Berkeley) news release by Robert Sanders and which originated the news item, provides more detail and history,

CRISPR-Cas12a, one of the DNA-cutting proteins revolutionizing biology today, has an unexpected side effect that makes it an ideal enzyme for simple, rapid and accurate disease diagnostics.

(iStock)

Cas12a, discovered in 2015 and originally called Cpf1, is like the well-known Cas9 protein that UC Berkeley’s Jennifer Doudna and colleague Emmanuelle Charpentier turned into a powerful gene-editing tool in 2012.

CRISPR-Cas9 has supercharged biological research in a mere six years, speeding up exploration of the causes of disease and sparking many potential new therapies. Cas12a was a major addition to the gene-cutting toolbox, able to cut double-stranded DNA at places that Cas9 can’t, and, because it leaves ragged edges, perhaps easier to use when inserting a new gene at the DNA cut.

But co-first authors Janice Chen, Enbo Ma and Lucas Harrington in Doudna’s lab discovered that when Cas12a binds and cuts a targeted double-stranded DNA sequence, it unexpectedly unleashes indiscriminate cutting of all single-stranded DNA in a test tube.

Most of the DNA in a cell is in the form of a double-stranded helix, so this is not necessarily a problem for gene-editing applications. But it does allow researchers to use a single-stranded “reporter” molecule with the CRISPR-Cas12a protein, which produces an unambiguous fluorescent signal when Cas12a has found its target.

“We continue to be fascinated by the functions of bacterial CRISPR systems and how mechanistic understanding leads to opportunities for new technologies,” said Doudna, a professor of molecular and cell biology and of chemistry and a Howard Hughes Medical Institute investigator.

The new DETECTR system based on CRISPR-Cas12a can analyze cells, blood, saliva, urine and stool to detect genetic mutations, cancer and antibiotic resistance as well as diagnose bacterial and viral infections. Target DNA is amplified by RPA to make it easier for Cas12a to find it and bind, unleashing indiscriminate cutting of single-stranded DNA, including DNA attached to a fluorescent marker (gold star) that tells researchers that Cas12a has found its target.

The UC Berkeley researchers, along with their colleagues at UC San Francisco, will publish their findings Feb. 15 [2018] via the journal Science’s fast-track service, First Release.

The researchers developed a diagnostic system they dubbed the DNA Endonuclease Targeted CRISPR Trans Reporter, or DETECTR, for quick and easy point-of-care detection of even small amounts of DNA in clinical samples. It involves adding all reagents in a single reaction: CRISPR-Cas12a and its RNA targeting sequence (guide RNA), fluorescent reporter molecule and an isothermal amplification system called recombinase polymerase amplification (RPA), which is similar to polymerase chain reaction (PCR). When warmed to body temperature, RPA rapidly multiplies the number of copies of the target DNA, boosting the chances Cas12a will find one of them, bind and unleash single-strand DNA cutting, resulting in a fluorescent readout.

The UC Berkeley researchers tested this strategy using patient samples containing human papilloma virus (HPV), in collaboration with Joel Palefsky’s lab at UC San Francisco. Using DETECTR, they were able to demonstrate accurate detection of the “high-risk” HPV types 16 and 18 in samples infected with many different HPV types.

“This protein works as a robust tool to detect DNA from a variety of sources,” Chen said. “We want to push the limits of the technology, which is potentially applicable in any point-of-care diagnostic situation where there is a DNA component, including cancer and infectious disease.”

The indiscriminate cutting of all single-stranded DNA, which the researchers discovered holds true for all related Cas12 molecules, but not Cas9, may have unwanted effects in genome editing applications, but more research is needed on this topic, Chen said. During the transcription of genes, for example, the cell briefly creates single strands of DNA that could accidentally be cut by Cas12a.

The activity of the Cas12 proteins is similar to that of another family of CRISPR enzymes, Cas13a, which chew up RNA after binding to a target RNA sequence. Various teams, including Doudna’s, are developing diagnostic tests using Cas13a that could, for example, detect the RNA genome of HIV.

(Infographic by the Howard Hughes Medical Institute)

These new tools have been repurposed from their original role in microbes where they serve as adaptive immune systems to fend off viral infections. In these bacteria, Cas proteins store records of past infections and use these “memories” to identify harmful DNA during infections. Cas12a, the protein used in this study, then cuts the invading DNA, saving the bacteria from being taken over by the virus.

The chance discovery of Cas12a’s unusual behavior highlights the importance of basic research, Chen said, since it came from a basic curiosity about the mechanism Cas12a uses to cleave double-stranded DNA.

“It’s cool that, by going after the question of the cleavage mechanism of this protein, we uncovered what we think is a very powerful technology useful in an array of applications,” Chen said.

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

CRISPR-Cas12a target binding unleashes indiscriminate single-stranded DNase activity by Janice S. Chen, Enbo Ma, Lucas B. Harrington, Maria Da Costa, Xinran Tian, Joel M. Palefsky, Jennifer A. Doudna. Science 15 Feb 2018: eaar6245 DOI: 10.1126/science.aar6245

This paper is behind a paywall.

Science in Muslim universities report, a science and Islam exhibit, and a debate about science and Islam

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The story of science in the Muslim world is extraordinary, influencing science to this day, and is not well known even within its own community. The days when Muslim or Islamic scientists led the world are long gone and that is cause for concern. An Oct. 29, 2015 Malaysian Industry-Government Group for High Technology press release on EurekAlert argues that universities in Muslim countries must reinvent themselves to transform society and achieve scientific excellence,

A Task Force of international experts, formed by the Muslim World Science Initiative, today released a report [Science at Universities of the Muslim World] on the state of science at universities of the Muslim world.

…

To assess the state of science at universities of the Muslim world, the Task Force reviewed the rankings of Muslim-world’s universities globally, scientific production (number of papers published and citations), the level of spending on research and development (R&D), female participation in the scientific workforce, and other indicators.

The results were compared to those of countries deemed comparable in terms of gross domestic product (GDP) per capita, e.g. Brazil, Israel, Spain, South Africa, and South Korea.

The Task Force noted recent improvements in scientific publishing across a number of countries and a relatively healthy gender ratio among university students, even though the overall state of science in the Muslim World remains ‘poor,’ as depicted by

the disproportionately small number of Nobel Laureates

the small number of universities in top global rankings

the low spending on R&D, and

the abysmal performance of pre-university students on math and science tests

Seeking to assess if universities were the ‘main culprits’ in this sorry state of affairs, the Task Force highlighted significant challenges at the Universities of the Muslim World.

In particular, the Task Force lamented the fact that science education in most Organization of Islamic Cooperation (OIC) member countries was extremely narrow in focus and did little to enable students to think critically, especially beyond their respective domains of specialty.

The Task Force calls for broad liberal education for scientists and engineers to enable them to function effectively in addressing complex multi-disciplinary challenges that the world faces today.

The Task Force also noted that self-censorship was often practiced in the selection of topics to be taught, particularly regarding controversial subjects such as the theory of evolution.

The Task Force called for the introduction and systematic study of philosophy of science and history of the sciences of the Muslim ‘Golden Age’ and beyond for students to navigate and develop a perspective on these difficult disciplinary boundaries and overlaps. The language of instruction also created significant challenges.

Faculty members were also ill-trained to teach using cutting-edge methods such as inquiry-based science education and had little autonomy to innovate.

While the Task Force called for greater autonomy for the universities, it also emphasized that they must become meritocracies and aspire for true scientific excellence rather than playing for temporary gains in numbers or rankings. It also calls for zero tolerance on plagiarism and other forms of academic misconduct.

The Report of the Task Force includes: a foreword by the Chair, Tan Sri Zakri Abdul Hamid, the main assessment and recommendations, and individual essays written by the Task Force members on issues, including

Science, Society & the University

Are universities of the Muslim world helping spread a culture of science through society?

Should Religion Be Kept Out of the Science Classroom?

STEM Education and the Muslim Gender Divide and

The Need of Liberal Education for Science and Engineering

The Task Force is putting out an open call for universities across the Muslim world to join a voluntary Network of Excellence of Universities for Science (NEXUS), to be launched early next year.

This peer group will be managed by the task force and housed in Tan Sri Zakri’s office. NEXUS will run summer schools for university administrators, monitor the progress of reforms at participating universities, and issue a peer report card that will assess the performance of the universities in meeting milestones, thus recognizing and inspiring further improvements. True transformation will require much broader action from ministries, regulators and funding agencies, and these may be the most resistant to change.

Releasing the Report of the Task Force, Tan Sri Zakri Abdul Hamid stressed that “universities must reinvent themselves to lead the scientific reforms in the Muslim World, and as they do so they must embrace key ideas of merit and transparency, engagement with society, and pedagogical and curricular innovation.”

Professor Nidhal Guessoum, the Task Force’s Convenor, noted that “Task Force members strongly believe that the most appropriate venue for action on our recommendations is the university itself. The most essential ingredient in creating excellence in science and science teaching at a university is a realization, within a university’s highest leadership and its faculty, of the need to give up the old and dated ways, renew the purpose, and re-write the genetic code of their university.

Dr. Athar Osama, the Director of the Project noted that “the purpose of Muslim World Science Initiative is to jumpstart a dialogue within the society on critical issues at the intersection of science, society, and Islam. The Task Force has done a commendable job in laying the groundwork for a very important conversation about our universities.”

The divide between science/technology/engineering/mathematics (STEM) education and other fields of interest such as social sciences, the arts, and the humanities may be larger in the Islamic world (and to some extent reversed with humanities looking down on science) but it is a problem elsewhere, often expressed as a form of snobbery, as I alluded to in my Aug. 7, 2015 posting titled: Science snobbery and the problem of accessibility.

An Oct. 28, 2015 Nature essay about Islam, science, and the report by Nidhal Guessou and Athar Osama (two members of the Task Force; Note: Links have been removed) provides more context,

The Islamic civilization lays claim to the world’s oldest continually operational university. The University of Qarawiyyin was founded in Fes, Morocco, in ad 859, at the beginning of an Islamic Golden Age. Despite such auspicious beginnings, universities in the region are now in dire straits, as demonstrated by a report we have authored, released this week (see go.nature.com/korli3).

The 57 countries of the Muslim world — those with a Muslim-majority population, and part of the Organisation of Islamic Cooperation (OIC) — are home to nearly 25% of the world’s people. But as of 2012, they had contributed only 1.6% of the world’s patents, 6% of its academic publications, and 2.4% of the global research expenditure1, 2.

The authors note problems and at least one success with regard to curriculum (from the Nature essay; Note: Links have been removed),

Science classes themselves have serious problems. The textbooks used in OIC universities are often imported from the United States or Europe. Although the content is of a high standard, they assume a Western experience and use English or French as the language of instruction. This disadvantages many students, and creates a disconnect between their education and culture. To encourage the production of higher-quality, local textbooks and other academic material, universities need to reward staff for producing these at least as much as they do for research publication.

Some basic facts are seen as controversial, and marginalized. Evolution, for example, is usually taught only to biology students, often as “a theory”, and is rarely connected to the rest of the body of knowledge. One ongoing study has found, for example, that most Malaysian physicians and medical students reject evolution (see go.nature.com/38cswo). Evolution needs to be taught widely and shown to be compatible with Islam and its culture6. Teaching the philosophy and history of science would help, too.

The global consensus is that enquiry-based science education fosters the deepest understanding of scientific concepts and laws. But in most OIC universities, lecture-based teaching still prevails. Exceptions are rare. One is the Petroleum Institute, an engineering university in Abu Dhabi, UAE, where the faculty has created a hands-on experience with positive results on student interest and enrolment, particularly of women.

For anyone interested in the full report, it can be requested from the Muslim Science website.

One final comment, here’s the list of task force members in the Oct. 29, 2015 news release which includes someone from Mauritius (my father was born there),

Tan Sri Zakri Abdul Hamid, Science Advisor to Prime Minister of Malaysia, Chair of the Task Force on Science at the Universities of the Muslim World

Prof. Nidhal Guessoum, American University of Sharjah, UAE, Convenor of the Task Force on Science at Universities of the Muslim World

Dr. Mohammad Yusoff Sulaiman, President and CEO, MiGHT, Malaysia, Co-Convenor of the Task Force on Science at Universities of the Muslim World.

Dr. Moneef Zou’bi, Executive Director, Islamic World Academy of Science (IAS)

Prof. Adil Najam, Dean Frederick S. Pardee School of Global Studies, Boston University and former Vice Chancellor, Lahore University of Management Sciences (LUMS)

Prof. Ameenah Gurib-Fakim, Fellow of IAS, President of the Republic of Mauritius, and Professor at University of Mauritius

Prof. Mustafa El-Tayeb, President , Future University, Khartoum, Sudan

Prof. Abdur Razak Dzulkifli, President of International Association of Universities (IAU), and former Vice Chancellor USM, Malaysia

Dr. Nadia Alhasani, Dean of Student Life (formerly Dean of Women in Science and Engineering (WiSE), The Petroleum Institute, Abu Dhabi, UAE

Prof. Jamal Mimouni, Professor, University of Constantine-1, Algeria

Dr. Dato Lee Yee Cheong, Chair ISTIC Governing Board / Chair IAP SEP Global Council

Prof. Michael Reiss, Professor of Science Education, UCL Institute of Education, University College, London, Expert Advisor to the Muslim-Science.Com Task Force on Science at Universities of the Muslim World

Prof. Bruce Alberts, Professor of Biochemistry, University of California, San Francisco; President Emeritus, National Academy of Sciences, and Recipient, 2014 US Presidential Medal of Science, Expert Advisor to the Muslim-Science.Com Task Force on Science at Universities of the Muslim World

Professor Shoaib S. H. Zaidi, Professor and Dean of School of Sciences and Engineering, Habib University, Karachi

Dr. Athar Osama, Founder Muslim World Science Initiative, and Project Director of the Task Forces Project.

1001 inventions exhibit

Reading about this report reminded me of a news item from five years ago when the London (UK) Science Museum launched the global tour of an exhibition titled, 1001 Inventions: Discover the Muslim Heritage in Our World,

This show is still making its way around the world with the latest stop, as of Oct. 20, 2015, at the Library of Alexandria in Egypt.

A Jan. 21, 2010 article by Nick Higham and Margaret Ryan for BBC (British Broadcasting Corporation) news online describes some of the exhibit highlights,

From about 700 to 1700, many of history’s finest scientists and technologists were to be found in the Muslim world.

In Christian Europe the light of scientific inquiry had largely been extinguished with the collapse of the Roman empire. But it survived, and indeed blazed brightly, elsewhere.

From Moorish Spain across North Africa to Damascus, Baghdad, Persia and all the way to India, scientists in the Muslim world were at the forefront of developments in medicine, astronomy, engineering, hydraulics, mathematics, chemistry, map-making and exploration.

…

Salim Al-Hassani, a former professor of engineering at Umist (University of Manchester Institute of Science and Technology) is a moving force behind the exhibition, 1001 Inventions.

…

Visitors to the exhibition will be greeted by a 20 ft high replica of a spectacular clock designed in 1206 by the inventor Al-Jazari.

It incorporates elements from many cultures, representing the different cultural and scientific traditions which combined and flowed through the Muslim world.

The clock’s base is an elephant, representing India; inside the elephant the water-driven works of the clock derive from ancient Greece.

A Chinese dragon swings down from the top of the clock to mark the hours. At the top is a phoenix, representing ancient Egypt.

Sitting astride the elephant and inside the framework of the clock are automata, or puppets, wearing Arab turbans.

Elsewhere in the exhibition are displays devoted to water power, the spread of education (one of the world’s first universities was founded by a Muslim woman, Fatima al-Fihri), Muslim architecture and its influence on the modern world and Muslim explorers and geographers.

There is a display of 10th Century surgeons’ instruments, a lifesize model of a man called Abbas ibn Firnas, allegedly the first person to have flown with wings, and a model of the vast 100 yard-long junk commanded by the Muslim Chinese navigator, Zheng He.

The description of the exhibition items is compelling.

Science and the modern world debate (Humanism and Islam)

Yasmin Khan has written up a transcript of sorts in a Nov. 6, 2015 posting on the Guardian science blogs about a science debate (which took place Wednesday, Oct. 28, 2015 in London, UK) where Humanist and Islamic perspectives were being discussed (Note: Links have been removed),

Two important figures came head-to-head at Conway Hall, to discuss Islamic versus Humanist perspectives on science and the modern world. Jim Al-Khalili made the final public appearance of his term as president of the British Humanist Association during this stimulating, and at times provoking, debate with Ziauddin Sardar, chair of the Muslim Institute.

Al-Khalili advocated the values of the European Enlightenment, arguing that ever since the “Age of Reason” took hold during the 18th century, Humanists have looked to science instead of religion to explore and comprehend the world. Sardar upheld the view that it is the combination of faith and reason that offers a fuller understanding of the world, maintaining that it was this worldview that enabled the development of science in the Islamic golden Age.

A practising Muslim, Sardar is on an independent mission to promote rational, considered thought in interpreting the Qur’an. He explained that when he came to the UK from Pakistan, he found comfort in the familiar language of mathematics, which set him on a trajectory to train as a physicist: “God doesn’t need me, I need him. It makes me a better person and a better scientist”, he said.

…

In short, Sardar’s view is that although human knowledge at times converges with the Qur’an, the text should certainly not be treated as a scientific encyclopaedia. In support of this view, Sardar lamented the emergence of the I’jaz movement, which insists the Qur’an contains descriptions of modern scientific phenomena ranging from quantum mechanics to accurate descriptions of the stages of embryology and geology. In Sardar’s opinion, this stems from insecurity and a personal need to vindicate Islam to others.

Jim Al-Khalili agreed that ascribing literal meanings to religious texts can be perilous and that these verses should be interpreted more metaphorically. Likewise, when Einstein famously said “God does not play dice” he was using a figure of speech to acknowledge that there are things we don’t yet understand but this shouldn’t stop us from trying to find out more.

Whilst Al-Khalili is a staunch atheist, he adopts what he describes as an “accommodationist” approach in his interactions with people of religious faith: “I don’t think people who believe in God are irrational, I just don’t see a need to believe there is a purpose for why things are the way they are.” Born in Bagdad, Al-Khalili grew up in Iraq. His mother was Christian and his father was Shia, but he never heard them quarrel about religion. By the time he reached his teens he felt that he had distanced himself from needing any form of spirituality and his subsequent scientific training cemented this worldview. He asserted that his core values are empathy, humility and respect, without being driven by a reward in an afterlife: “It’s not just people of religious faith that have a moral compass – morality is what makes us human.”

I encourage you to read Khan’s piece (Nov. 6, 2015 posting) in its entirety as she provides historical and contemporary context to what seems to have been a fascinating and nuanced debate. Plus, there’s a bit of a bonus at the end where Khan is described as the producer of Sindbad Sci-Fi, a website where they are Reimagining Arab Science Fiction. From the website’s About page,

Sindbad Sci-Fi is an initiative for spurring the discovery of and engagement with Arab Science Fiction through dialogue. Our aim is to sustain a growing community of interest through brokering face-to-face and online discussion, building new partnerships and project collaborations along the way.

Many of us know and love Sindbad the sailor as the fictional sailor from the Arabian Book of One Thousand and One Nights, considered as being an early composite work of proto-science fiction and fantasy. His extraordinary voyages led him to adventures in magical places whilst meeting monsters and encountering supernatural phenomena.

Sindbad Sci-Fi is reviving Sindbad’s adventurous spirit for exploration and discovery. Join us as we continue star trekking across the Middle East, North Africa, South Asia and beyond. Together, we will boldly go where no one else has gone before!

I’m pretty sure somebody associated with this site is a Star Trek fan.

Cells as capacitors and resistors concept is key to smart bandages

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Bandages that can detect bedsores as they are forming are a distinct possibility with advances in flexible electronics and miniaturization according to researchers at the University of California at Berkeley and the University of California at San Francisco. From a March 17, 2015 University of California at Berkeley news release by Sarah Yang (also on EurekAlert),

Engineers at the University of California, Berkeley, are developing a new type of bandage that does far more than stanch the bleeding from a paper cut or scraped knee. Thanks to advances in flexible electronics, the researchers, in collaboration with colleagues at UC San Francisco, have created a new “smart bandage” that uses electrical currents to detect early tissue damage from pressure ulcers, or bedsores, before they can be seen by human eyes – and while recovery is still possible.

“We set out to create a type of bandage that could detect bedsores as they are forming, before the damage reaches the surface of the skin,” said Michel Maharbiz, a UC Berkeley associate professor of electrical engineering and computer sciences and head of the smart-bandage project. “We can imagine this being carried by a nurse for spot-checking target areas on a patient, or it could be incorporated into a wound dressing to regularly monitor how it’s healing.”

The researchers exploited the electrical changes that occur when a healthy cell starts dying. They tested the thin, non-invasive bandage on the skin of rats and found that the device was able to detect varying degrees of tissue damage consistently across multiple animals.

Bed sores are a big problem now and I imagine that as the population ages and more people find themselves in ill health, the problem will increase (from the news release),

Tackling a growing health problem

The findings, to be published Tuesday, March 17, in the journal Nature Communications, could provide a major boost to efforts to stem a health problem that affects an estimated 2.5 million U.S. residents at an annual cost of $11 billion.

Pressure ulcers, or bedsores, are injuries that can result after prolonged pressure cuts off adequate blood supply to the skin. Areas that cover bony parts of the body, such as the heels, hips and tailbone, are common sites for bedsores. Patients who are bedridden or otherwise lack mobility are most at risk.

“By the time you see signs of a bedsore on the surface of the skin, it’s usually too late,” said Dr. Michael Harrison, a professor of surgery at UCSF and a co-investigator of the study. “This bandage could provide an easy early-warning system that would allow intervention before the injury is permanent. If you can detect bedsores early on, the solution is easy. Just take the pressure off.”

Bedsores are associated with deadly septic infections, and recent research has shown that odds of a hospital patient dying are 2.8 times higher when they have pressure ulcers. The growing prevalence of diabetes and obesity has increased the risk factors for bedsores.

“The genius of this device is that it’s looking at the electrical properties of the tissue to assess damage. We currently have no other way to do that in clinical practice,” said Harrison. “It’s tackling a big problem that many people have been trying to solve in the last 50 years. As a clinician and someone who has struggled with this clinical problem, this bandage is great.”

The electrical components and their role in detecting bed sores is fascinating (from the news release),

Cells as capacitors and resistors

The researchers printed an array of dozens of electrodes onto a thin, flexible film. They discharged a very small current between the electrodes to create a spatial map of the underlying tissue based upon the flow of electricity at different frequencies, a technique called impedance spectroscopy.

The researchers pointed out that a cell’s membrane is relatively impermeable when functioning properly, thus acting like an insulator to the cell’s conductive contents and drawing the comparison to a capacitor. As a cell starts to die, the integrity of the cell wall starts to break down, allowing electrical signals to leak through, much like a resistor.

“Our device is a comprehensive demonstration that tissue health in a living organism can be locally mapped using impedance spectroscopy,” said study lead author Sarah Swisher, a Ph.D. candidate in electrical engineering and computer sciences at UC Berkeley.

To mimic a pressure wound, the researchers gently squeezed the bare skin of rats between two magnets. They left the magnets in place for one or three hours while the rats resumed normal activity. The resumption of blood flow after the magnets were removed caused inflammation and oxidative damage that accelerated cell death. The smart bandage was used to collect data once a day for at least three days to track the progress of the wounds.

The smart bandage was able to detect changes in electrical resistance consistent with increased membrane permeability, a mark of a dying cell. Not surprisingly, one hour of pressure produced mild, reversible tissue damage while three hours of pressure produced more serious, permanent injury.

Promising future

“One of the things that makes this work novel is that we took a comprehensive approach to understanding how the technique could be used to observe developing wounds in complex tissue,” said Swisher. “In the past, people have used impedance spectroscopy for cell cultures or relatively simple measurements in tissue. What makes this unique is extending that to detect and extract useful information from wounds developing in the body. That’s a big leap.”

Maharbiz said the outlook for this and other smart bandage research is bright.

“As technology gets more and more miniaturized, and as we learn more and more about the responses the body has to disease and injury, we’re able to build bandages that are very intelligent,” he said. “You can imagine a future where the bandage you or a physician puts on could actually report a lot of interesting information that could be used to improve patient care.”

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

Impedance sensing device enables early detection of pressure ulcers in vivo by Sarah L. Swisher, Monica C. Lin, Amy Liao, Elisabeth J. Leeflang, Yasser Khan, Felippe J. Pavinatto, Kaylee Mann, Agne Naujokas, David Young, Shuvo Roy, Michael R. Harrison, Ana Claudia Arias, Vivek Subramanian, & Michel M. Maharbiz. Nature Communications 6, Article number: 6575 doi:10.1038/ncomms7575 Published 17 March 2015

This paper is behind a paywall but there is a free preview available via ReadCube Access.

Finally, one of the researchers describes the work in this 1 min. 31 secs. video,

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