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Turning brain-controlled wireless electronic prostheses into reality plus some ethical points

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Researchers at Stanford University (California, US) believe they have a solution for a problem with neuroprosthetics (Note: I have included brief comments about neuroprosthetics and possible ethical issues at the end of this posting) according an August 5, 2020 news item on ScienceDaily,

The current generation of neural implants record enormous amounts of neural activity, then transmit these brain signals through wires to a computer. But, so far, when researchers have tried to create wireless brain-computer interfaces to do this, it took so much power to transmit the data that the implants generated too much heat to be safe for the patient. A new study suggests how to solve his problem — and thus cut the wires.

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Caption: Photo of a current neural implant, that uses wires to transmit information and receive power. New research suggests how to one day cut the wires. Credit: Sergey Stavisky

An August 3, 2020 Stanford University news release (also on EurekAlert but published August 4, 2020) by Tom Abate, which originated the news item, details the problem and the proposed solution,

Stanford researchers have been working for years to advance a technology that could one day help people with paralysis regain use of their limbs, and enable amputees to use their thoughts to control prostheses and interact with computers.

The team has been focusing on improving a brain-computer interface, a device implanted beneath the skull on the surface of a patient’s brain. This implant connects the human nervous system to an electronic device that might, for instance, help restore some motor control to a person with a spinal cord injury, or someone with a neurological condition like amyotrophic lateral sclerosis, also called Lou Gehrig’s disease.

The current generation of these devices record enormous amounts of neural activity, then transmit these brain signals through wires to a computer. But when researchers have tried to create wireless brain-computer interfaces to do this, it took so much power to transmit the data that the devices would generate too much heat to be safe for the patient.

Now, a team led by electrical engineers and neuroscientists Krishna Shenoy, PhD, and Boris Murmann, PhD, and neurosurgeon and neuroscientist Jaimie Henderson, MD, have shown how it would be possible to create a wireless device, capable of gathering and transmitting accurate neural signals, but using a tenth of the power required by current wire-enabled systems. These wireless devices would look more natural than the wired models and give patients freer range of motion.

Graduate student Nir Even-Chen and postdoctoral fellow Dante Muratore, PhD, describe the team’s approach in a Nature Biomedical Engineering paper.

The team’s neuroscientists identified the specific neural signals needed to control a prosthetic device, such as a robotic arm or a computer cursor. The team’s electrical engineers then designed the circuitry that would enable a future, wireless brain-computer interface to process and transmit these these carefully identified and isolated signals, using less power and thus making it safe to implant the device on the surface of the brain.

To test their idea, the researchers collected neuronal data from three nonhuman primates and one human participant in a (BrainGate) clinical trial.

As the subjects performed movement tasks, such as positioning a cursor on a computer screen, the researchers took measurements. The findings validated their hypothesis that a wireless interface could accurately control an individual’s motion by recording a subset of action-specific brain signals, rather than acting like the wired device and collecting brain signals in bulk.

The next step will be to build an implant based on this new approach and proceed through a series of tests toward the ultimate goal.

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

Power-saving design opportunities for wireless intracortical brain–computer interfaces by Nir Even-Chen, Dante G. Muratore, Sergey D. Stavisky, Leigh R. Hochberg, Jaimie M. Henderson, Boris Murmann & Krishna V. Shenoy. Nature Biomedical Engineering (2020) DOI: https://doi.org/10.1038/s41551-020-0595-9 Published: 03 August 2020

This paper is behind a paywall.

Comments about ethical issues

As I found out while investigating, ethical issues in this area abound. My first thought was to look at how someone with a focus on ability studies might view the complexities.

My ‘go to’ resource for human enhancement and ethical issues is Gregor Wolbring, an associate professor at the University of Calgary (Alberta, Canada). his profile lists these areas of interest: ability studies, disability studies, governance of emerging and existing sciences and technologies (e.g. neuromorphic engineering, genetics, synthetic biology, robotics, artificial intelligence, automatization, brain machine interfaces, sensors) and more.

I can’t find anything more recent on this particular topic but I did find an August 10, 2017 essay for The Conversation where he comments on technology and human enhancement ethical issues where the technology is gene-editing. Regardless, he makes points that are applicable to brain-computer interfaces (human enhancement), Note: Links have been removed),

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Ability expectations have been and still are used to disable, or disempower, many people, not only people seen as impaired. They’ve been used to disable or marginalize women (men making the argument that rationality is an important ability and women don’t have it). They also have been used to disable and disempower certain ethnic groups (one ethnic group argues they’re smarter than another ethnic group) and others.

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A recent Pew Research survey on human enhancement revealed that an increase in the ability to be productive at work was seen as a positive. What does such ability expectation mean for the “us” in an era of scientific advancements in gene-editing, human enhancement and robotics?

Which abilities are seen as more important than others?

The ability expectations among “us” will determine how gene-editing and other scientific advances will be used.

And so how we govern ability expectations, and who influences that governance, will shape the future. Therefore, it’s essential that ability governance and ability literacy play a major role in shaping all advancements in science and technology.

One of the reasons I find Gregor’s commentary so valuable is that he writes lucidly about ability and disability as concepts and poses what can be provocative questions about expectations and what it is to be truly abled or disabled. You can find more of his writing here on his eponymous (more or less) blog.

Ethics of clinical trials for testing brain implants

This October 31, 2017 article by Emily Underwood for Science was revelatory,

In 2003, neurologist Helen Mayberg of Emory University in Atlanta began to test a bold, experimental treatment for people with severe depression, which involved implanting metal electrodes deep in the brain in a region called area 25 [emphases mine]. The initial data were promising; eventually, they convinced a device company, St. Jude Medical in Saint Paul, to sponsor a 200-person clinical trial dubbed BROADEN.

This month [October 2017], however, Lancet Psychiatry reported the first published data on the trial’s failure. The study stopped recruiting participants in 2012, after a 6-month study in 90 people failed to show statistically significant improvements between those receiving active stimulation and a control group, in which the device was implanted but switched off.

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… a tricky dilemma for companies and research teams involved in deep brain stimulation (DBS) research: If trial participants want to keep their implants [emphases mine], who will take responsibility—and pay—for their ongoing care? And participants in last week’s meeting said it underscores the need for the growing corps of DBS researchers to think long-term about their planned studies.

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… participants bear financial responsibility for maintaining the device should they choose to keep it, and for any additional surgeries that might be needed in the future, Mayberg says. “The big issue becomes cost [emphasis mine],” she says. “We transition from having grants and device donations” covering costs, to patients being responsible. And although the participants agreed to those conditions before enrolling in the trial, Mayberg says she considers it a “moral responsibility” to advocate for lower costs for her patients, even it if means “begging for charity payments” from hospitals. And she worries about what will happen to trial participants if she is no longer around to advocate for them. “What happens if I retire, or get hit by a bus?” she asks.

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There’s another uncomfortable possibility: that the hypothesis was wrong [emphases mine] to begin with. A large body of evidence from many different labs supports the idea that area 25 is “key to successful antidepressant response,” Mayberg says. But “it may be too simple-minded” to think that zapping a single brain node and its connections can effectively treat a disease as complex as depression, Krakauer [John Krakauer, a neuroscientist at Johns Hopkins University in Baltimore, Maryland] says. Figuring that out will likely require more preclinical research in people—a daunting prospect that raises additional ethical dilemmas, Krakauer says. “The hardest thing about being a clinical researcher,” he says, “is knowing when to jump.”

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Brain-computer interfaces, symbiosis, and ethical issues

This was the most recent and most directly applicable work that I could find. From a July 24, 2019 article by Liam Drew for Nature Outlook: The brain,

“It becomes part of you,” Patient 6 said, describing the technology that enabled her, after 45 years of severe epilepsy, to halt her disabling seizures. Electrodes had been implanted on the surface of her brain that would send a signal to a hand-held device when they detected signs of impending epileptic activity. On hearing a warning from the device, Patient 6 knew to take a dose of medication to halt the coming seizure.

“You grow gradually into it and get used to it, so it then becomes a part of every day,” she told Frederic Gilbert, an ethicist who studies brain–computer interfaces (BCIs) at the University of Tasmania in Hobart, Australia. “It became me,” she said. [emphasis mine]

Gilbert was interviewing six people who had participated in the first clinical trial of a predictive BCI to help understand how living with a computer that monitors brain activity directly affects individuals psychologically1. Patient 6’s experience was extreme: Gilbert describes her relationship with her BCI as a “radical symbiosis”.

Symbiosis is a term, borrowed from ecology, that means an intimate co-existence of two species for mutual advantage. As technologists work towards directly connecting the human brain to computers, it is increasingly being used to describe humans’ potential relationship with artificial intelligence.

Interface technologies are divided into those that ‘read’ the brain to record brain activity and decode its meaning, and those that ‘write’ to the brain to manipulate activity in specific regions and affect their function.

Commercial research is opaque, but scientists at social-media platform Facebook are known to be pursuing brain-reading techniques for use in headsets that would convert users’ brain activity into text. And neurotechnology companies such as Kernel in Los Angeles, California, and Neuralink, founded by Elon Musk in San Francisco, California, predict bidirectional coupling in which computers respond to people’s brain activity and insert information into their neural circuitry. [emphasis mine]

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Already, it is clear that melding digital technologies with human brains can have provocative effects, not least on people’s agency — their ability to act freely and according to their own choices. Although neuroethicists’ priority is to optimize medical practice, their observations also shape the debate about the development of commercial neurotechnologies.

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Neuroethicists began to note the complex nature of the therapy’s side effects. “Some effects that might be described as personality changes are more problematic than others,” says Maslen [Hannah Maslen, a neuroethicist at the University of Oxford, UK]. A crucial question is whether the person who is undergoing stimulation can reflect on how they have changed. Gilbert, for instance, describes a DBS patient who started to gamble compulsively, blowing his family’s savings and seeming not to care. He could only understand how problematic his behaviour was when the stimulation was turned off.

Such cases present serious questions about how the technology might affect a person’s ability to give consent to be treated, or for treatment to continue. [emphases mine] If the person who is undergoing DBS is happy to continue, should a concerned family member or doctor be able to overrule them? If someone other than the patient can terminate treatment against the patient’s wishes, it implies that the technology degrades people’s ability to make decisions for themselves. It suggests that if a person thinks in a certain way only when an electrical current alters their brain activity, then those thoughts do not reflect an authentic self.

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To observe a person with tetraplegia bringing a drink to their mouth using a BCI-controlled robotic arm is spectacular. [emphasis mine] This rapidly advancing technology works by implanting an array of electrodes either on or in a person’s motor cortex — a brain region involved in planning and executing movements. The activity of the brain is recorded while the individual engages in cognitive tasks, such as imagining that they are moving their hand, and these recordings are used to command the robotic limb.

If neuroscientists could unambiguously discern a person’s intentions from the chattering electrical activity that they record in the brain, and then see that it matched the robotic arm’s actions, ethical concerns would be minimized. But this is not the case. The neural correlates of psychological phenomena are inexact and poorly understood, which means that signals from the brain are increasingly being processed by artificial intelligence (AI) software before reaching prostheses.[emphasis mine]

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But, he [Philipp Kellmeyer, a neurologist and neuroethicist at the University of Freiburg, Germany] says, using AI tools also introduces ethical issues of which regulators have little experience. [emphasis mine] Machine-learning software learns to analyse data by generating algorithms that cannot be predicted and that are difficult, or impossible, to comprehend. This introduces an unknown and perhaps unaccountable process between a person’s thoughts and the technology that is acting on their behalf.

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Maslen is already helping to shape BCI-device regulation. She is in discussion with the European Commission about regulations it will implement in 2020 that cover non-invasive brain-modulating devices that are sold straight to consumers. [emphases mine; Note: There is a Canadian company selling this type of product, MUSE] Maslen became interested in the safety of these devices, which were covered by only cursory safety regulations. Although such devices are simple, they pass electrical currents through people’s scalps to modulate brain activity. Maslen found reports of them causing burns, headaches and visual disturbances. She also says clinical studies have shown that, although non-invasive electrical stimulation of the brain can enhance certain cognitive abilities, this can come at the cost of deficits in other aspects of cognition.

Regarding my note about MUSE, the company is InteraXon and its product is MUSE.They advertise the product as “Brain Sensing Headbands That Improve Your Meditation Practice.” The company website and the product seem to be one entity, Choose Muse. The company’s product has been used in some serious research papers they can be found here. I did not see any research papers concerning safety issues.

Getting back to Drew’s July 24, 2019 article and Patient 6,

… He [Gilbert] is now preparing a follow-up report on Patient 6. The company that implanted the device in her brain to help free her from seizures went bankrupt. The device had to be removed.

… Patient 6 cried as she told Gilbert about losing the device. … “I lost myself,” she said.

“It was more than a device,” Gilbert says. “The company owned the existence of this new person.”

I strongly recommend reading Drew’s July 24, 2019 article in its entirety.

Finally

It’s easy to forget that in all the excitement over technologies ‘making our lives better’ that there can be a dark side or two. Some of the points brought forth in the articles by Wolbring, Underwood, and Drew confirmed my uneasiness as reasonable and gave me some specific examples of how these technologies raise new issues or old issues in new ways.

What I find interesting is that no one is using the term ‘cyborg’, which would seem quite applicable.There is an April 20, 2012 posting here titled ‘My mother is a cyborg‘ where I noted that by at lease one definition people with joint replacements, pacemakers, etc. are considered cyborgs. In short, cyborgs or technology integrated into bodies have been amongst us for quite some time.

Interestingly, no one seems to care much when insects are turned into cyborgs (can’t remember who pointed this out) but it is a popular area of research especially for military applications and search and rescue applications.

I’ve sometimes used the term ‘machine/flesh’ and or ‘augmentation’ as a description of technologies integrated with bodies, human or otherwise. You can find lots on the topic here however I’ve tagged or categorized it.

Amongst other pieces you can find here, there’s the August 8, 2016 posting, ‘Technology, athletics, and the ‘new’ human‘ featuring Oscar Pistorius when he was still best known as the ‘blade runner’ and a remarkably successful paralympic athlete. It’s about his efforts to compete against able-bodied athletes at the London Olympic Games in 2012. It is fascinating to read about technology and elite athletes of any kind as they are often the first to try out ‘enhancements’.

Gregor Wolbring has a number of essays on The Conversation looking at Paralympic athletes and their pursuit of enhancements and how all of this is affecting our notions of abilities and disabilities. By extension, one has to assume that ‘abled’ athletes are also affected with the trickle-down effect on the rest of us.

Regardless of where we start the investigation, there is a sameness to the participants in neuroethics discussions with a few experts and commercial interests deciding on how the rest of us (however you define ‘us’ as per Gregor Wolbring’s essay) will live.

This paucity of perspectives is something I was getting at in my COVID-19 editorial for the Canadian Science Policy Centre. My thesis being that we need a range of ideas and insights that cannot be culled from small groups of people who’ve trained and read the same materials or entrepreneurs who too often seem to put profit over thoughtful implementations of new technologies. (See the PDF May 2020 edition [you’ll find me under Policy Development]) or see my May 15, 2020 posting here (with all the sources listed.)

As for this new research at Stanford, it’s exciting news, which raises questions, as it offers the hope of independent movement for people diagnosed as tetraplegic (sometimes known as quadriplegic.)

Nanoparticles and the gut health of major living species of animals

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A July 27, 2020 news item on Nanowerk announces research into gut health described as seminal (Note: A link has been removed),

An international team of scientists has completed the first ever study into the potential impact of naturally occurring and man-made nanoparticles on the health of all types of the major living species of animals.

Conceived by researchers at the University of Plymouth, as part of the EU [European Union] Nanofase project, the study assessed how the guts of species from honey bees to humans could protect against the bioaccumulation and toxicological effects of engineered nanomaterials (ENMs) found within the environment.

A July 27, 2020 University of Plymouth press release, which originated the news item, provides more detail,

It showed that the digestive systems of many species have evolved to act as a barrier guarding against the absorption of potentially damaging particles.

However, invertebrates such as earthworms also have roving cells within their guts, which can take up ENMs and transfer them to the gut wall.

This represents an additional risk for many invertebrate species where the particles can be absorbed via these roving cells, with consequent effects on internal organs having the potential to cause lasting damage.

Fortunately, this process is not replicated in humans and other vertebrate animals, however there is still the potential for nanomaterials to have a negative impact through the food chain.

The study, published in the July [2020] edition of Environmental Science: Nano, involved scientists from the UK, the Netherlands, Slovenia and Portugal and focused on particles measuring up to 100 nanometres (around 1/10 millionth of a metre).

It combined existing and new research into species including insects and other invertebrates, fish, birds, and mammals, as well as identifying knowledge gaps on reptiles and amphibians. The study provides the first comprehensive overview of how differences in gut structure can affect the impact of ENMs across the animal kingdom.

Richard Handy, Professor of Environmental Toxicology at the University of Plymouth and the study’s senior author, said:

“This is a seminal piece work that combines nearly 100 years of zoology research with our current understanding of nanotechnology.

“The threats posed by engineered nanomaterials are becoming better known, but this study provides the first comprehensive and species-level assessment of how they might pose current and future threats. It should set the foundations for understanding the dietary hazard in the animal kingdom.”

Nanomaterials come in three forms – naturally occurring, incidentally occurring from human activities, and deliberately manufactured – and their use has increased exponentially in the last decade.

They have consistently found new applications in a wide variety of industrial sectors, including electrical appliances, medicines, cleaning products and textiles.

Professor Handy, who has advised organisations including the Organisation for Economic Co-operation and Development and the United States National Nanotechnology Initiative, added:

“Nanoparticles are far too small for the human eye to see but that doesn’t mean they cannot cause harm to living species. The review element of this study has shown they have actually been written about for many decades, but it is only recently that we have begun to understand the various ways they occur and now the extent to which they can be taken up. Our new EU project, NanoHarmony, looks to build on that knowledge and we are currently working with Public Health England and others to expand our method for detecting nanomaterials in tissues for food safety and other public health matters.”

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

The gut barrier and the fate of engineered nanomaterials: a view from comparative physiology by Meike van der Zande, Anita Jemec Kokalj, David J. Spurgeon, Susana Loureiro, Patrícia V. Silva, Zahra Khodaparast, Damjana Drobne, Nathaniel J. Clark, Nico W. van den Brink, Marta Baccaro, Cornelis A. M. van Gestel, Hans Bouwmeester and Richard D. Handy. Environmental Science: Nano, Issue 7 (July 2020) DOI: 10.1039/D0EN00174K First published 27 Apr 2020

This article is open access.

If you’re curious about Nanofase (Nanomaterial FAte and Speciation in the Environment), there’s more here and there’s more about NanoHarmony here.

Filmmaking beetles wearing teeny, tiny wireless cameras

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Researchers at the University of Washington have developed a tiny camera that can ride aboard an insect. Here a Pinacate beetle explores the UW campus with the camera on its back. Credit: Mark Stone/University of Washington

Scientists at Washington University have created a removable wireless camera backpack for beetles and for tiny robots resembling beetles. I’m embedding a video shot by a beetle later in this post with a citation and link for the paper, near the end of this post where you’ll also find links to my other posts on insects and technology.

As for the latest on insects and technology, there’s a July 15, 2020 news item on ScienceDaily,

In the movie “Ant-Man,” the title character can shrink in size and travel by soaring on the back of an insect. Now researchers at the University of Washington have developed a tiny wireless steerable camera that can also ride aboard an insect, giving everyone a chance to see an Ant-Man view of the world.

The camera, which streams video to a smartphone at 1 to 5 frames per second, sits on a mechanical arm that can pivot 60 degrees. This allows a viewer to capture a high-resolution, panoramic shot or track a moving object while expending a minimal amount of energy. To demonstrate the versatility of this system, which weighs about 250 milligrams — about one-tenth the weight of a playing card — the team mounted it on top of live beetles and insect-sized robots.

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A July 15, 2020 University of Washington news release (also on EurekAlert), which originated the news item, provides more technical detail (although I still have a few questions) about the work,

“We have created a low-power, low-weight, wireless camera system that can capture a first-person view of what’s happening from an actual live insect or create vision for small robots,” said senior author Shyam Gollakota, a UW associate professor in the Paul G. Allen School of Computer Science & Engineering. “Vision is so important for communication and for navigation, but it’s extremely challenging to do it at such a small scale. As a result, prior to our work, wireless vision has not been possible for small robots or insects.”

Typical small cameras, such as those used in smartphones, use a lot of power to capture wide-angle, high-resolution photos, and that doesn’t work at the insect scale. While the cameras themselves are lightweight, the batteries they need to support them make the overall system too big and heavy for insects — or insect-sized robots — to lug around. So the team took a lesson from biology.

“Similar to cameras, vision in animals requires a lot of power,” said co-author Sawyer Fuller, a UW assistant professor of mechanical engineering. “It’s less of a big deal in larger creatures like humans, but flies are using 10 to 20% of their resting energy just to power their brains, most of which is devoted to visual processing. To help cut the cost, some flies have a small, high-resolution region of their compound eyes. They turn their heads to steer where they want to see with extra clarity, such as for chasing prey or a mate. This saves power over having high resolution over their entire visual field.”

To mimic an animal’s vision, the researchers used a tiny, ultra-low-power black-and-white camera that can sweep across a field of view with the help of a mechanical arm. The arm moves when the team applies a high voltage, which makes the material bend and move the camera to the desired position. Unless the team applies more power, the arm stays at that angle for about a minute before relaxing back to its original position. This is similar to how people can keep their head turned in one direction for only a short period of time before returning to a more neutral position.

“One advantage to being able to move the camera is that you can get a wide-angle view of what’s happening without consuming a huge amount of power,” said co-lead author Vikram Iyer, a UW doctoral student in electrical and computer engineering. “We can track a moving object without having to spend the energy to move a whole robot. These images are also at a higher resolution than if we used a wide-angle lens, which would create an image with the same number of pixels divided up over a much larger area.”

The camera and arm are controlled via Bluetooth from a smartphone from a distance up to 120 meters away, just a little longer than a football field.

The researchers attached their removable system to the backs of two different types of beetles — a death-feigning beetle and a Pinacate beetle. Similar beetles have been known to be able to carry loads heavier than half a gram, the researchers said.

“We made sure the beetles could still move properly when they were carrying our system,” said co-lead author Ali Najafi, a UW doctoral student in electrical and computer engineering. “They were able to navigate freely across gravel, up a slope and even climb trees.”

The beetles also lived for at least a year after the experiment ended. [emphasis mine]

“We added a small accelerometer to our system to be able to detect when the beetle moves. Then it only captures images during that time,” Iyer said. “If the camera is just continuously streaming without this accelerometer, we could record one to two hours before the battery died. With the accelerometer, we could record for six hours or more, depending on the beetle’s activity level.”

The researchers also used their camera system to design the world’s smallest terrestrial, power-autonomous robot with wireless vision. This insect-sized robot uses vibrations to move and consumes almost the same power as low-power Bluetooth radios need to operate.

The team found, however, that the vibrations shook the camera and produced distorted images. The researchers solved this issue by having the robot stop momentarily, take a picture and then resume its journey. With this strategy, the system was still able to move about 2 to 3 centimeters per second — faster than any other tiny robot that uses vibrations to move — and had a battery life of about 90 minutes.

While the team is excited about the potential for lightweight and low-power mobile cameras, the researchers acknowledge that this technology comes with a new set of privacy risks.

“As researchers we strongly believe that it’s really important to put things in the public domain so people are aware of the risks and so people can start coming up with solutions to address them,” Gollakota said.

Applications could range from biology to exploring novel environments, the researchers said. The team hopes that future versions of the camera will require even less power and be battery free, potentially solar-powered.

“This is the first time that we’ve had a first-person view from the back of a beetle while it’s walking around. There are so many questions you could explore, such as how does the beetle respond to different stimuli that it sees in the environment?” Iyer said. “But also, insects can traverse rocky environments, which is really challenging for robots to do at this scale. So this system can also help us out by letting us see or collect samples from hard-to-navigate spaces.”

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Johannes James, a UW mechanical engineering doctoral student, is also a co-author on this paper. This research was funded by a Microsoft fellowship and the National Science Foundation.

I’m surprised there’s no funding from a military agency as the military and covert operation applications seem like an obvious pairing. In any event, here’s a link to and a citation for the paper,

Wireless steerable vision for live insects and insect-scale robots by Vikram Iyer, Ali Najafi, Johannes James, Sawyer Fuller, and Shyamnath Gollakota. Science Robotics 15 Jul 2020: Vol. 5, Issue 44, eabb0839 DOI: 10.1126/scirobotics.abb0839

This paper is behind a paywall.

Video and links

As promised, here’s the video the scientists have released,

These posts feature some fairly ruthless uses of the insects.

  1. The first mention of insects and technology here is in a July 27, 2009 posting titled: Nanotechnology enables robots and human enhancement: part 4. The mention is in the second to last paragraph of the post. Then,.
  2. A November 23, 2011 post titled: Cyborg insects and trust,
  3. A January 9, 2012 post titled: Controlling cyborg insects,
  4. A June 26, 2013 post titled: Steering cockroaches in the lab and in your backyard—cutting edge neuroscience, and, finally,
  5. An April 11, 2014 post titled: Computerized cockroaches as precursors to new healing techniques.

As for my questions (how do you put the backpacks on the beetles? is there a strap, is it glue, is it something else? how heavy is the backpack and camera? how old are the beetles you use for this experiment? where did you get the beetles from? do you have your own beetle farm where you breed them?), I’ll see if I can get some answers.

Norwegian Institute for Water Research (NIVA) releases study on silver and titanium nanomaterials in wastewater

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It turns out that silver and titanium nanomaterials (e.g. silver nanoparticles washed out of athletic clothing) in wastewater may have ‘negative’ and ‘positive’ effects on freshwater and marine life depending on the species.

A November 18, 2019 news item on Nanowerk provides an introduction to the research (Note: Links have been removed),

You may not always think about it when you do your laundry or flush the toilet; but whatever you eat, wear or apply on your skin ends up in wastewater and eventually reaches the environment. The use of nanoparticles in consumer products like textiles, foods and personal care products is increasing.

What is so special about nanoparticles, is their tiny size: One nanometer is one billionth of a meter. The small size gives nanoparticles unique and novel properties compared to their bigger counterparts and may for example reach locations that bigger particles cannot reach.
Further, pristine nanoparticles behave differently from nanoparticles in the environment. In the environment, nanoparticles are transformed by interacting and forming aggregates with other particles, elements or solids, and thereby obtain other physicochemical properties.

The transformation of these tiny particles in wastewater treatment processes and their effect on freshwater and marine organisms, have largely been unknown.
Increased mortality of marine crustaceans.

In a study (“Ecotoxicological Effects of Transformed Silver and Titanium Dioxide Nanoparticles in the Effluent from a Lab-Scale Wastewater Treatment System”) conducted at the Norwegian Institute for Water Research (NIVA), Anastasia Georgantzopoulou and colleagues from NIVA and SINTEF investigated how silver and titanium dioxide nanoparticles behave in wastewater treatment plants, and how marine and freshwater organisms are affected by them.

Exposure to treated wastewater did not have any adverse effects on the freshwater crustacean Daphnia magna. (Photo: NIVA)

A November 18, 2019 NIVA press release, which originated the news item, fills in the details,

The researchers made a laboratory-scale wastewater treatment plant, using sludge from a wastewater treatment plant in Norway. They added environmentally relevant concentrations of silver (Ag) and titanium dioxide (TiO2) nanoparticles over a 5-week period and used the treated wastewater to assess the effects of transformed nanoparticles on freshwater and marine organisms, as well as on gill cells from rainbow trout.

The experiment demonstrated contrasting effects on the two crustacean species. For the marine copepod (Tisbe battagliai), mortality increased by 20-45%, whereas exposure to ttreated wastewater did not have any adverse effects on the freshwater crustacean (Daphnia magna).

“These differences are probably due, at least partly, to the two species’ different feeding habits, in combination with the fact that the nanoparticles showed a strong association to solids present in the wastewater”, Georgantzopoulou says, and explains:

“Daphnia magna is an organism that filters water for food, whereas the marine copepod feeds on bottom surfaces – like effluent solids that have settled out from the water. The bottom feeding crustacean is therefore more likely to ingest nanoparticles, and thereby be affected by solid-associated nanoparticles”. 

Effects on algal species

Nanoparticle-containing treated wastewater also affected algal growth, but the two algae species did not have a common response: The marine algae (Skeletonema pseudocostatum) responded with a 20-40 % growth inhibition, while the algal growth of the freshwater algae (Raphidocelis subcapitata) was actually stimulated, by a 40 % increase, accompanied by increased cell aggregation. The latter is probably some kind of a defense mechanism, aiming to decrease the surface area exposed to toxic particles.

“The results from our study indicate that algal responses to the treated wastewater exposure are species-dependent. This is possibly due to differences in algal cell size, surface area, and cell wall composition”, the NIVA researcher explains.

Increased permeability of fish gill cells

The researchers also found effects of silver and titanium nanoparticles on fish gill cells using an in vitro gill cell line model. As large amounts of water are passing through the gills, and they constitute a barrier to the external environment, this organ is highly exposed to water-borne contaminants, including nanoparticles.

“Exposure to nanoparticle-containing wastewater lead to an increase in reactive oxygen species, a group of molecules that can easily react with and damage cells. This was followed by increased permeability of the gill cells, leading to a compromised barrier function”, Georgantzopoulou says.

“However, the concentrations of silver and titanium nanoparticles in the treated wastewater were too low to fully account for the effects on cell permeability alone. The wastewater effluent is a complex mixture of materials, and the permeability response is probably caused by a combination of the presence of nanoparticles and other stressors”, Georgantzopoulou adds.

Wastewater treatment-transformation of nanoparticles

“We carried out this study on wastewater treatment plant-transformed nanoparticles, and compared them to pristine nanoparticles, as the former is more relevant to what is actually happening in the environment. The increased toxicity of the transformed nanomaterials observed in the study indicates that the effects cannot be predicted by assessing the effects of nanomaterials in their pristine form and highlights the importance of understanding their behavior, environmental transformation and interaction with organisms. Future studies should take nanoparticle transformation into account and focus on a more relevant experimental exposure conditions incorporating transformed nanoparticles in more long-term impact studies to provide a better understanding of their potential impacts”, Georgantzopoulou concludes.

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

Ecotoxicological Effects of Transformed Silver and Titanium Dioxide Nanoparticles in the Effluent from a Lab-Scale Wastewater Treatment System by Anastasia Georgantzopoulou, Patricia Almeida Carvalho, Christian Vogelsang, Mengstab Tilahun, Kuria Ndungu, Andy M. Booth, Kevin V. Thomas, Ailbhe Macken. Environ. Sci. Technol. 2018, 52, 16, 9431-9441 DOI: https://doi.org/10.1021/acs.est.8b01663 Publication Date:July 26, 2018 Copyright © 2018 American Chemical Society

This paper is behind a paywall.

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.

…

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
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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]
…

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.

Effective safety strategies for CRISPR (clustered regularly interspaced short palindromic repeats) gene drive experiments

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It’s very peculiar being able to understand each word individually in clustered regularly interspaced short palindromic repeats (CRISPR) but not being able to puzzle out much meaning other than the widely known ‘it’s a gene editor’.

Regardless, CRISPR is a powerful gene editing tool and that can lead to trouble. Even before CRISPR, we’ve had some genetic accidents. Perhaps the best known is the ‘killer bee’ or Africanized bee (from its Wikepedia entry),

The Africanized bee, also known as the Africanised honey bee, and known colloquially as “killer bee”, is a hybrid of the western honey bee species (Apis mellifera), produced originally by cross-breeding [emphasis mine] of the East African lowland honey bee (A. m. scutellata) with various European honey bees such as the Italian honey bee A. m. ligustica and the Iberian honey bee A. m. iberiensis.

The Africanized honey bee was first introduced to Brazil in 1956 in an effort to increase honey production, but 26 swarms escaped quarantine in 1957 [emphasis mine]. Since then, the hybrid has spread throughout South America and arrived in North America in 1985. Hives were found in South Texas of the United States in 1990.

Africanized bees are typically much more defensive than other varieties of honey bee, and react to disturbances faster than European honey bees. They can chase a person a quarter of a mile (400 m); they have killed some 1,000 humans, with victims receiving ten times more stings than from European honey bees. They have also killed horses and other animals.

…

Getting back to how powerful CRISPR is, a group of scientists has developed a set of strategies for safeguarding gene drive experiments (from a January 22, 2019 eLife press release also on EurekAlert),

Researchers have demonstrated for the first time how two molecular strategies can safeguard CRISPR gene drive experiments in the lab, according to a study published today in eLife.

Their findings, first reported on bioRxiv, suggest that scientists can effectively use synthetic target sites and split drives to conduct gene drive research, without the worry of causing an accidental spread throughout a natural population.

Gene drives, such as those trialled in malaria mosquitoes, are genetic packages designed to spread among populations. They do this via a process called ‘drive conversion’, where the Cas9 enzyme and a molecule called guide RNA (gRNA) cut at a certain site in the genome. The drive is then copied in when the DNA break is repaired.

“CRISPR-based gene drives have sparked both enthusiasm and deep concerns due to their potential for genetically altering entire species,” explains first author Jackson Champer, Postdoctoral Fellow in the Department of Biological Statistics and Computational Biology at Cornell University, New York. “This raises the question about our ability to prevent the unintended spread of such drives from the laboratory into the natural world.

“Current strategies for avoiding accidental spread involve physically confining drive-containing organisms. However, it is uncertain whether this sufficiently reduces the likelihood of any accidental escape into the wild, given the possibility of human error.”

Two molecular safeguarding strategies have recently been proposed that go beyond simply confining research organisms. The first is synthetic target site drive, which homes into engineered genomic sites that are absent in wild organisms. The second is split drive, where the drive construct lacks a type of enzyme called the endonuclease and relies instead on one engineered into a distant site.

“The nature of these strategies means that they should prevent an efficient spread outside of their respective laboratory lines,” Champer adds. “We wanted to see if they both had a similar performance to standard homing drives, and if they would therefore be suitable substitutes in early gene-drive research.”

To do this, the team designed and tested three synthetic target site drives in the fruit fly Drosophila melanogaster. Each drive targeted an enhanced green fluorescent protein (EGFP) gene introduced at one of three different sites in the genome. For split drives, they designed a drive construct that targeted the X-linked gene yellow and lacked Cas9.

Their analyses revealed that CRISPR gene drives with synthetic target sites such as EGFP show similar behaviour to standard drives, and can therefore be used for most testing in place of these drives. The split drives demonstrated similar performance, and also allow for natural sequences to be targeted in situations where the use of synthetic targets is difficult. These include population-suppression drives that require the targeting of naturally occurring genes

“Based on our findings, we suggest these safeguarding strategies should be adopted consistently in the development and testing of future gene drives,” says senior author Philipp Messer, Assistant Professor in the Department of Biological Statistics and Computational Biology at Cornell University. “This will be important for large-scale cage experiments aimed at improving our understanding of the expected population dynamics of candidate drives. Ultimately, this understanding will be crucial for discussing the feasibility and risks of releasing successful drives into the wild, for example to reduce malaria and other vector-borne diseases.”

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

Molecular safeguarding of CRISPR gene drive experiments by Jackson Champer, Joan Chung, Yoo Lim Lee, Chen Liu, Emily Yang, Zhaoxin Wen, Andrew G Clark, Philipp W Messer. DOI: 10.7554/eLife.41439 Short Report Jan 22, 2019

This paper is open access. For anyone who doesn’t mind reading an earlier version of a paper you can find it at bioRxiv, at https://www.biorxiv.org/content/early/2018/09/08/411876.

elife, which i’ve mentioned here here before in a February 8, 2018 posting is a (from their About eLife webpage)

… non-profit organisation inspired by research funders and led by scientists. Our mission is to help scientists accelerate discovery by operating a platform for research communication that encourages and recognises the most responsible behaviours in science.

Searchable database for hazardous nanomaterials and a Graphene Verification Programme

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I have two relatively recent news bits about nanomaterials, the second being entirely focused on graphene.

Searchable database

A July 9, 2019 news item on Nanowerk announces a means of finding out what hazards may be associated with 300 different nanomaterials (Note: A Link has been removed),

A new search tool for nanomaterials has been published on the European Union Observatory for Nanomaterials (EUON) website. It will enable regulators to form a better view of available data and give consumers access to chemicals safety information.

The tool combines data submitted by companies in their REACH registrations [Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) ], data collected about nanomaterials used as ingredients in cosmetic products under the Cosmetics Regulation and data from the public national nanomaterial inventories of Belgium and France.

…

A July 3, 2019 EUON press release, which originated the news item, provides a bit more detail,

The EUON’s search brings data from these sources together in one place, allowing users to easily search for nanomaterials that are currently on the EU market. The results are linked to ECHA’s [European Chemicals Agency] database of chemicals registered in the EU and, for the first time, summarised information about the substances, their properties as well as detailed safety and characterisation data can be easily found.

Background

While there are over 300 nanomaterials on the EU market, 37 are currently covered by an existing registration under REACH. The information requirements for REACH were revised last year with explicit obligations for nanomaterials manufactured in or imported to the EU. The new requirements enter into force in January 2020 and will result in more publicly available information.

The EUON aims to increase the transparency of information available to the public on the safety and markets of nanomaterials in the EU. A key aim of the observatory is to create a one-stop shop for information, where EU citizens and stakeholders including NGOs, industry, and regulators can all easily find accessible and relevant safety information on nanomaterials on the EU market.

Here’s the searchable database.

Graphene verification

There was a bit of a scandal about fake graphene in the Fall of 2018 (my May 28, 2019 posting gives details). Dexter Johnson provides additional insight and information about the launch of a new graphene verification programme and news of a slightly older graphene verification programme in his July 9, 2019 article for the Nanoclast blog on the IEEE (Institute of Electrical and Electronics Engineers) website (Note: Links have been removed),

Last year [2018], the graphene community was rocked by a series of critical articles that appeared in some high-profile journals. First there was an Advanced Material’s article with the rather innocuously title: “The Worldwide Graphene Flake Production”. It was perhaps the follow-up article that appeared in the journal Nature that really shook things up with its incendiary title: “The war on fake graphene”.

In these two articles it was revealed that material that had been claimed to be high-quality (and high-priced) graphene was little more than graphite powder. Boosted by their appearance in high-impact journals, these articles threatened the foundations of the graphene marketplace.

But while these articles triggered a lot of hand wringing among the buyers and sellers of graphene, it’s not clear that their impact extended much beyond the supply chain of graphene. Whether or not graphene has aggregated back to being graphite is one question. An even bigger one is whether or not consumers are actually being sold a better product on the basis that it incorporates graphene.

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Dexter details some of the issues from the consumer’s perspective (Note: Links have been removed),

Consumer products featuring graphene today include everything from headphones to light bulbs. Consequently, there is already confusion among buyers about the tangible benefits graphene is supposed to provide. And of course the situation becomes even worse if the graphene sold to make products may not even be graphene: how are consumers supposed to determine whether graphene infuses their products with anything other than a buzzword?

Another source of confusion arises because when graphene is incorporated into a product it is effectively a different animal from graphene in isolation. There is ample scientific evidence that graphene when included in a material matrix, like a polymer or even paper, can impart new properties to the materials. “You can transfer some very useful properties of graphene into other materials by adding graphene, but just because the resultant material contains graphene it does not mean it will behave like free-standing graphene, explains Tom Eldridge, of UK-based Fullerex, a consultancy that provides companies with information on how to include graphene in a material matrix

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The rest of Dexter’s posting goes on to mention two new graphene verification progammes (producer and product) available through The Graphene Council. As for what the council is, there’s this from council’s About webpage,

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The Graphene Council was founded in 2013 with a mission to serve the global community of graphene professionals. Today, The Graphene Council is the largest community in the world for graphene researchers, academics, producers, developers, investors, nanotechnologists, regulatory agencies, research institutes, material science specialists and even the general public. We reach more than 50,000 people with an interest in this amazing material. 

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Interestingly the council’s offices are located in the US state of North Carolina. (I would have guessed that its headquarters would be in the UK, given the ‘ownership’ the UK has been attempting to establish over graphene Let me clarify, by ownership I mean the Brits want to be recognized as dominant or preeminent in graphene research and commercialization.)

The council’s first verified graphene producer is a company based in the UK as can be seen in an April 1, 2019 posting by council director Terrance Barkan on the council’s blog,

The Graphene Council is pleased to announce that Versarien plc is the first graphene company in the world to successfully complete the Verified Graphene Producer™ program, an independent, third party verification system that involves a physical inspection of the production facilities, a review of the entire production process, a random sample of product material and rigorous characterization and testing by a first class, international materials laboratory.

The Verified Graphene Producer™ program is an important step to bring transparency and clarity to a rapidly changing and opaque market for graphene materials, providing graphene customers with a level of confidence that has not existed before.

“We are pleased to have worked with the National Physical Laboratory (NPL) in the UK, regarded as one of the absolute top facilities for metrology and graphene characterization in the world.
 
They have provided outstanding analytical expertise for the materials testing portion of the program including Raman Spectroscopy, XPS, AFM and SEM testing services.” stated Terrance Barkan CAE, Executive Director of The Graphene Council.
 
Andrew Pollard, Science Area Leader of the Surface Technology Group, National Physical Laboratory, said: “In order to develop real-world products that can benefit from the ‘wonder material’, graphene, we first need to fully understand its properties, reliably and reproducibly.
 
“Whilst international measurement standards are currently being developed, it is critical that material characterisation is performed to the highest possible level.
 
As the UK’s National Measurement Institute (NMI) with a focus on developing the metrology of graphene and related 2D materials, we aim to be an independent third party in the testing of graphene material for companies and associations around the world, such as The Graphene Council.” 
 
Neill Ricketts, CEO of Versarien said: “We are delighted that Versarien is the first graphene producer in the world to successfully complete the Graphene Council’s Verified Graphene Producer™ programme.”
 
“This is a huge validation of our technology and will enable our partners and potential customers to have confidence that the graphene we produce meets globally accepted standards.”
 
“There are many companies that claim to be graphene producers, but to enjoy the benefits that this material can deliver requires high quality, consistent product to be supplied.  The Verified Producer programme is designed to verify that our production facilities, processes and tested material meet the stringent requirements laid down by The Graphene Council.”

“I am proud that Versarien has been independently acclaimed as a Verified Graphene Producer™ and look forward to making further progress with our collaboration partners and numerous other parties that we are in discussions with.”

James Baker CEng FIET, the CEO of Graphene@Manchester (which includes coordinating the efforts of the National Graphene Institute and the Graphene Engineering and Innovation Centre [GEIC]) stated: “We applaud The Graphene Council for promoting independent third party verification for graphene producers that is supported by world class metrology and characterization services.”

“This is an important contribution to the commercialization of graphene as an industrial material and are proud to have The Graphene Council as an Affiliate Member of the Graphene Engineering and Innovation Centre (GEIC) here in Manchester ”.

Successful commercialization of graphene materials requires not only the ability to produce graphene to a declared specification but to be able to do so at a commercial scale.
It is nearly impossible for a graphene customer to verify the type of material they are receiving without going through an expensive and time consuming process of having sample materials fully characterized by a laboratory that has the equipment and expertise to test graphene.

The Verified Graphene Producer™ program developed by The Graphene Councilprovides a level of independent inspection and verification that is not available anywhere else.

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As for the “Verified Graphene Product” programme mentioned in Dexter’s article (it’s not included in the excerpts here), I can’t find any sign of it ion the council’s website.

In six hours billions of plastic nanoparticles accumulate in marine organisms

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For the sake of comparison, I wish they’d thought to include an image of a giant scallop that hadn’t been used in the research (I have an ‘unplastic’ giant scallop image at the end of this posting),

Caption: These are some of the scallops used as part of the current research. Credit: University of Plymouth

But, they did do this,

A scan showing nanoplastic particles accumulated within the scallop’s gills (GI), kidney (K), gonad (GO), intestine (I), hepatopancreas (HP) and muscle (M). Credit: University of Plymouth [downloaded from https://phys.org/news/2018-12-billions-nanoplastics-accumulate-marine-hours.html]

A December 3, 2018 news item on phys.org announces the research,

A ground-breaking study has shown it takes a matter of hours for billions of minute plastic nanoparticles to become embedded throughout the major organs of a marine organism.

The research, led by the University of Plymouth, examined the uptake of nanoparticles by a commercially important mollusc, the great scallop (Pecten maximus).

After six hours exposure in the laboratory, billions of particles measuring 250nm (around 0.00025mm) had accumulated within the scallop’s intestines.

However, considerably more even smaller particles measuring 20nm (0.00002mm) had become dispersed throughout the body including the kidney, gill, muscle and other organs.

A December 3, 2018 University of Plymouth press release (also on EurekAlert), which originated the news item, adds more detail,

The study is the first to quantify the uptake of nanoparticles at predicted environmentally relevant conditions, with previous research having been conducted at far higher concentrations than scientists believe are found in our oceans.

Dr Maya Al Sid Cheikh, Postdoctoral Research Fellow at the University of Plymouth, led the study. She said: “For this experiment, we needed to develop an entirely novel scientific approach. We made nanoparticles of plastic in our laboratories and incorporated a label so that we could trace the particles in the body of the scallop at environmentally relevant concentrations. The results of the study show for the first time that nanoparticles can be rapidly taken up by a marine organism, and that in just a few hours they become distributed across most of the major organs.”

Professor Richard Thompson OBE, Head of the University’s International Marine Litter Research Unit, added: “This is a ground breaking study, in terms of both the scientific approach and the findings. We only exposed the scallops to nanoparticles for a few hours and, despite them being transferred to clean conditions, traces were still present several weeks later. Understanding the dynamics of nanoparticle uptake and release, as well as their distribution in body tissues, is essential if we are to understand any potential effects on organisms. A key next step will be to use this approach to guide research investigating any potential effects of nanoparticles and in particular to consider the consequences of longer term exposures.”

Accepted for publication in the Environmental Science and Technology journal, the study also involved scientists from the Charles River Laboratories in Elphinstone, Scotland; the Institute Maurice la Montagne in Canada; and Heriot-Watt University.

It was conducted as part of RealRiskNano, a £1.1million project funded by the Natural Environment Research Council (NERC). Led by Heriot-Watt and Plymouth, it is exploring the effects which microscopic plastic particles can have on the marine environment.

In this study, the scallops were exposed to quantities of carbon-radiolabeled nanopolystyrene and after six hours, autoradiography was used to show the number of particles present in organs and tissue.

It was also used to demonstrate that the 20nm particles were no longer detectable after 14 days, whereas 250nm particles took 48 days to disappear.

Ted Henry, Professor of Environmental Toxicology at Heriot-Watt University, said: “Understanding whether plastic particles are absorbed across biological membranes and accumulate within internal organs is critical for assessing the risk these particles pose to both organism and human health. The novel use of radiolabelled plastic particles pioneered in Plymouth provides the most compelling evidence to date on the level of absorption of plastic particles in a marine organism.”

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

Uptake, Whole-Body Distribution, and Depuration of Nanoplastics by the Scallop Pecten maximus at Environmentally Realistic Concentrations by Maya Al-Sid-Cheikh, Steve J. Rowland, Karen Stevenson, Claude Rouleau, Theodore B. Henry, and Richard C. Thompson. Environ. Sci. Technol., Article ASAP DOI: 10.1021/acs.est.8b05266 Publication Date (Web): November 20, 2018

Copyright © 2018 American Chemical Society

This paper is behind a paywall.

‘Unplastic giant scallop’

The sea scallop (Placopecten magellanicus) has over 100 blue eyes along the edge of its mantle, with which it senses light intensity. This mollusk has the ability to scoot away from potential danger by flapping the two parts of its shell, like a swimming castenet. Credit: Dann Blackwood, USGS – http://www.sanctuaries.nos.noaa.gov/pgallery/pgstellwagen/living/living_17.html Public Domain

Stunning, isn’t it?

How do nanoparticles interact with the environment and with humans over time?

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I meant to get this piece published sooner but good intentions don’t get you far.

At Northwestern University, scientists have researched the impact engineered nanoparticles (ENPs) might have as they enter the food chain. An October 18, 2019 Northwestern University news release (also on EurekAlert) by Megan Fellman describes research on an investigation of ENPs and their interaction with living organisms,

Personal electronic devices — smartphones, computers, TVs, tablets, screens of all kinds — are a significant and growing source of the world’s electronic waste. Many of these products use nanomaterials, but little is known about how these modern materials and their tiny particles interact with the environment and living things.

Now a research team of Northwestern University chemists and colleagues from the national Center for Sustainable Nanotechnology has discovered that when certain coated nanoparticles interact with living organisms it results in new properties that cause the nanoparticles to become sticky. Fragmented lipid coronas form on the particles, causing them to stick together and grow into long kelp-like strands. Nanoparticles with 5-nanometer diameters form long structures that are microns in size in solution. The impact on cells is not known.

“Why not make a particle that is benign from the beginning?” said Franz M. Geiger, professor of chemistry in Northwestern’s Weinberg College of Arts and Sciences. He led the Northwestern portion of the research.

“This study provides insight into the molecular mechanisms by which nanoparticles interact with biological systems,” Geiger said. “This may help us understand and predict why some nanomaterial/ligand coating combinations are detrimental to cellular organisms while others are not. We can use this to engineer nanoparticles that are benign by design.”

Using experiments and computer simulations, the research team studied how gold nanoparticles wrapped in strings having positively charged beads interact with a variety of bilayer membrane models. The researchers found that a nearly circular layer of lipids forms spontaneously around the particles. Formation of these “fragmented lipid coronas” have never been seen before to form from membranes.

The study points to solving problems with chemistry. Scientists can use the findings to design a better ligand coating for nanoparticles that avoids the ammonium-phosphate interaction, which causes the aggregation. (Ligands are used in nanomaterials for layering.)

The results will be published Oct. 18 [2018] in the journal Chem.

Geiger is the study’s corresponding author. Other authors include scientists from the Center for Sustainable Nanotechnology’s other institutional partners. Based at the University of Wisconsin-Madison, the center studies engineered nanomaterials and their interaction with the environment, including biological systems — both the negative and positive aspects.

“The nanoparticles pick up parts of the lipid cellular membrane like a snowball rolling in a snowfield, and they become sticky,” Geiger said. “This unintended effect happens because of the presence of the nanoparticle. It can bring lipids to places in cells where lipids are not meant to be.”

The experiments were conducted in idealized laboratory settings that nevertheless are relevant to environments found during the late summer in a landfill — at 21-22 degrees Celsius and a couple feet below ground, where soil and groundwater mix and the food chain begins.

By pairing spectroscopic and imaging experiments with atomistic and coarse-grain simulations, the researchers identified that ion pairing between the lipid head groups of biological membranes and the polycations’ ammonium groups in the nanoparticle wrapping leads to the formation of fragmented lipid coronas. These coronas engender new properties, including composition and stickiness, to the particles with diameters below 10 nanometers.

The study’s insights help predict the impact that the increasingly widespread use of engineered nanomaterials has on the nanoparticles’ fate once they enter the food chain, which many of them may eventually do.

“New technologies and mass consumer products are emerging that feature nanomaterials as critical operational components,” Geiger said. “We can upend the existing paradigm in nanomaterial production towards one in which companies design nanomaterials to be sustainable from the beginning, as opposed to risking expensive product recalls — or worse — down the road.” [emphases mine]

Here’s an image illustrating the work,

Caption: This is a computer simulation of a lipid corona around a 5-nanometer nanoparticle showing ammonium-phosphate ion pairing. Credit: Northwestern University

The curious can find the paper here,

Lipid Corona Formation from Nanoparticle Interactions with Bilayers by Laura L. Olenick, Julianne M. Troiano, Ariane Vartanian, Eric S. Melby, Arielle C. Mensch, Leili Zhang, Jiewei Hong, Oluwaseun Mesele, Tian Qiu, Jared Bozich, Samuel Lohse, Xi Zhang, Thomas R. Kuech, Augusto Millevolte, Ian Gunsolus, Alicia C. McGeachy, Merve Doğangün, Tianzhe Li, Dehong Hu, Stephanie R. Walter, Aurash Mohaimani, Angela Schmoldt, Marco D. Torelli, Katherine R. Hurley, Joe Dalluge, Gene Chong, Z. Vivian Feng, Christy L. Haynes, Robert J. Hamers, Joel A. Pedersen, Qiang Cui, Rigoberto Hernandez, Rebecca Klaper, Galya Orr, Catherine J. Murphy, Franz M. Geiger. Chem Volume 4, ISSUE 11, P2709-2723, November 08, 2018 DOI:https://doi.org/10.1016/j.chempr.2018.09.018 Published:October 18, 2018

This paper is behind a paywall.

Gene editing and personalized medicine: Canada

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Back in the fall of 2018 I came across one of those overexcited pieces about personalized medicine and gene editing tha are out there. This one came from an unexpected source, an author who is a “PhD Scientist in Medical Science (Blood and Vasculature” (from Rick Gierczak’s LinkedIn profile).

It starts our promisingly enough although I’m beginning to dread the use of the word ‘precise’  where medicine is concerned, (from a September 17, 2018 posting on the Science Borealis blog by Rick Gierczak (Note: Links have been removed),

CRISPR-Cas9 technology was accidentally discovered in the 1980s when scientists were researching how bacteria defend themselves against viral infection. While studying bacterial DNA called clustered regularly interspaced short palindromic repeats (CRISPR), they identified additional CRISPR-associated (Cas) protein molecules. Together, CRISPR and one of those protein molecules, termed Cas9, can locate and cut precise regions of bacterial DNA. By 2012, researchers understood that the technology could be modified and used more generally to edit the DNA of any plant or animal. In 2015, the American Association for the Advancement of Science chose CRISPR-Cas9 as science’s “Breakthrough of the Year”.

Today, CRISPR-Cas9 is a powerful and precise gene-editing tool [emphasis mine] made of two molecules: a protein that cuts DNA (Cas9) and a custom-made length of RNA that works like a GPS for locating the exact spot that needs to be edited (CRISPR). Once inside the target cell nucleus, these two molecules begin editing the DNA. After the desired changes are made, they use a repair mechanism to stitch the new DNA into place. Cas9 never changes, but the CRISPR molecule must be tailored for each new target — a relatively easy process in the lab. However, it’s not perfect, and occasionally the wrong DNA is altered [emphasis mine].

Note that Gierczak makes a point of mentioning that CRISPR/Cas9 is “not perfect.” And then, he gets excited (Note: Links have been removed),

CRISPR-Cas9 has the potential to treat serious human diseases, many of which are caused by a single “letter” mutation in the genetic code (A, C, T, or G) that could be corrected by precise editing. [emphasis mine] Some companies are taking notice of the technology. A case in point is CRISPR Therapeutics, which recently developed a treatment for sickle cell disease, a blood disorder that causes a decrease in oxygen transport in the body. The therapy targets a special gene called fetal hemoglobin that’s switched off a few months after birth. Treatment involves removing stem cells from the patient’s bone marrow and editing the gene to turn it back on using CRISPR-Cas9. These new stem cells are returned to the patient ready to produce normal red blood cells. In this case, the risk of error is eliminated because the new cells are screened for the correct edit before use.

The breakthroughs shown by companies like CRISPR Therapeutics are evidence that personalized medicine has arrived. [emphasis mine] However, these discoveries will require government regulatory approval from the countries where the treatment is going to be used. In the US, the Food and Drug Administration (FDA) has developed new regulations allowing somatic (i.e., non-germ) cell editing and clinical trials to proceed. [emphasis mine]

The potential treatment for sickle cell disease is exciting but Gierczak offers no evidence that this treatment or any unnamed others constitute proof that “personalized medicine has arrived.” In fact, Goldman Sachs, a US-based investment bank, makes the case that it never will .

Cost/benefit analysis

Edward Abrahams, president of the Personalized Medicine Coalition (US-based), advocates for personalized medicine while noting in passing, market forces as represented by Goldman Sachs in his May 23, 2018 piece for statnews.com (Note: A link has been removed),

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One of every four new drugs approved by the Food and Drug Administration over the last four years was designed to become a personalized (or “targeted”) therapy that zeros in on the subset of patients likely to respond positively to it. That’s a sea change from the way drugs were developed and marketed 10 years ago.

Some of these new treatments have extraordinarily high list prices. But focusing solely on the cost of these therapies rather than on the value they provide threatens the future of personalized medicine.

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… most policymakers are not asking the right questions about the benefits of these treatments for patients and society. Influenced by cost concerns, they assume that prices for personalized tests and treatments cannot be justified even if they make the health system more efficient and effective by delivering superior, longer-lasting clinical outcomes and increasing the percentage of patients who benefit from prescribed treatments.

Goldman Sachs, for example, issued a report titled “The Genome Revolution.” It argues that while “genome medicine” offers “tremendous value for patients and society,” curing patients may not be “a sustainable business model.” [emphasis mine] The analysis underlines that the health system is not set up to reap the benefits of new scientific discoveries and technologies. Just as we are on the precipice of an era in which gene therapies, gene-editing, and immunotherapies promise to address the root causes of disease, Goldman Sachs says that these therapies have a “very different outlook with regard to recurring revenue versus chronic therapies.”

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Let’s just chew on this one (contemplate)  for a minute”curing patients may not be ‘sustainable business model’!”

Coming down to earth: policy

While I find Gierczak to be over-enthused, he, like Abrahams, emphasizes the importance of new policy, in his case, the focus is Canadian policy. From Gierczak’s September 17, 2018 posting (Note: Links have been removed),

In Canada, companies need approval from Health Canada. But a 2004 law called the Assisted Human Reproduction Act (AHR Act) states that it’s a criminal offence “to alter the genome of a human cell, or in vitroembryo, that is capable of being transmitted to descendants”. The Actis so broadly written that Canadian scientists are prohibited from using the CRISPR-Cas9 technology on even somatic cells. Today, Canada is one of the few countries in the world where treating a disease with CRISPR-Cas9 is a crime.

On the other hand, some countries provide little regulatory oversight for editing either germ or somatic cells. In China, a company often only needs to satisfy the requirements of the local hospital where the treatment is being performed. And, if germ-cell editing goes wrong, there is little recourse for the future generations affected.

The AHR Act was introduced to regulate the use of reproductive technologies like in vitrofertilization and research related to cloning human embryos during the 1980s and 1990s. Today, we live in a time when medical science, and its role in Canadian society, is rapidly changing. CRISPR-Cas9 is a powerful tool, and there are aspects of the technology that aren’t well understood and could potentially put patients at risk if we move ahead too quickly. But the potential benefits are significant. Updated legislation that acknowledges both the risks and current realities of genomic engineering [emphasis mine] would relieve the current obstacles and support a path toward the introduction of safe new therapies.

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Criminal ban on human gene-editing of inheritable cells (in Canada)

I had no idea there was a criminal ban on the practice until reading this January 2017 editorial by Bartha Maria Knoppers, Rosario Isasi, Timothy Caulfield, Erika Kleiderman, Patrick Bedford, Judy Illes, Ubaka Ogbogu, Vardit Ravitsky, & Michael Rudnicki for (Nature) npj Regenerative Medicine (Note: Links have been removed),

Driven by the rapid evolution of gene editing technologies, international policy is examining which regulatory models can address the ensuing scientific, socio-ethical and legal challenges for regenerative and personalised medicine.1 Emerging gene editing technologies, including the CRISPR/Cas9 2015 scientific breakthrough,2 are powerful, relatively inexpensive, accurate, and broadly accessible research tools.3 Moreover, they are being utilised throughout the world in a wide range of research initiatives with a clear eye on potential clinical applications. Considering the implications of human gene editing for selection, modification and enhancement, it is time to re-examine policy in Canada relevant to these important advances in the history of medicine and science, and the legislative and regulatory frameworks that govern them. Given the potential human reproductive applications of these technologies, careful consideration of these possibilities, as well as ethical and regulatory scrutiny must be a priority.4

With the advent of human embryonic stem cell research in 1978, the birth of Dolly (the cloned sheep) in 1996 and the Raelian cloning hoax in 2003, the environment surrounding the enactment of Canada’s 2004 Assisted Human Reproduction Act (AHRA) was the result of a decade of polarised debate,5 fuelled by dystopian and utopian visions for future applications. Rightly or not, this led to the AHRA prohibition on a wide range of activities, including the creation of embryos (s. 5(1)(b)) or chimeras (s. 5(1)(i)) for research and in vitro and in vivo germ line alterations (s. 5(1)(f)). Sanctions range from a fine (up to $500,000) to imprisonment (up to 10 years) (s. 60 AHRA).

In Canada, the criminal ban on gene editing appears clear, the Act states that “No person shall knowingly […] alter the genome of a cell of a human being or in vitro embryo such that the alteration is capable of being transmitted to descendants;” [emphases mine] (s. 5(1)(f) AHRA). This approach is not shared worldwide as other countries such as the United Kingdom, take a more regulatory approach to gene editing research.1 Indeed, as noted by the Law Reform Commission of Canada in 1982, criminal law should be ‘an instrument of last resort’ used solely for “conduct which is culpable, seriously harmful, and generally conceived of as deserving of punishment”.6 A criminal ban is a suboptimal policy tool for science as it is inflexible, stifles public debate, and hinders responsiveness to the evolving nature of science and societal attitudes.7 In contrast, a moratorium such as the self-imposed research moratorium on human germ line editing called for by scientists in December 20158 can at least allow for a time limited pause. But like bans, they may offer the illusion of finality and safety while halting research required to move forward and validate innovation.

On October 1st, 2016, Health Canada issued a Notice of Intent to develop regulations under the AHRA but this effort is limited to safety and payment issues (i.e. gamete donation). Today, there is a need for Canada to revisit the laws and policies that address the ethical, legal and social implications of human gene editing. The goal of such a critical move in Canada’s scientific and legal history would be a discussion of the right of Canadians to benefit from the advancement of science and its applications as promulgated in article 27 of the Universal Declaration of Human Rights9 and article 15(b) of the International Covenant on Economic, Social and Cultural Rights,10 which Canada has signed and ratified. Such an approach would further ensure the freedom of scientific endeavour both as a principle of a liberal democracy and as a social good, while allowing Canada to be engaged with the international scientific community.

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Even though it’s a bit old, I still recommend reading the open access editorial in full, if you have the time.

One last thing abut the paper, the acknowledgements,

Sponsored by Canada’s Stem Cell Network, the Centre of Genomics and Policy of McGill University convened a ‘think tank’ on the future of human gene editing in Canada with legal and ethics experts as well as representatives and observers from government in Ottawa (August 31, 2016). The experts were Patrick Bedford, Janetta Bijl, Timothy Caulfield, Judy Illes, Rosario Isasi, Jonathan Kimmelman, Erika Kleiderman, Bartha Maria Knoppers, Eric Meslin, Cate Murray, Ubaka Ogbogu, Vardit Ravitsky, Michael Rudnicki, Stephen Strauss, Philip Welford, and Susan Zimmerman. The observers were Geneviève Dubois-Flynn, Danika Goosney, Peter Monette, Kyle Norrie, and Anthony Ridgway.

Competing interests

The authors declare no competing interests.

Both McGill and the Stem Cell Network pop up again. A November 8, 2017 article about the need for new Canadian gene-editing policies by Tom Blackwell for the National Post features some familiar names (Did someone have a budget for public relations and promotion?),

It’s one of the most exciting, and controversial, areas of health science today: new technology that can alter the genetic content of cells, potentially preventing inherited disease — or creating genetically enhanced humans.

But Canada is among the few countries in the world where working with the CRISPR gene-editing system on cells whose DNA can be passed down to future generations is a criminal offence, with penalties of up to 10 years in jail.

This week, one major science group announced it wants that changed, calling on the federal government to lift the prohibition and allow researchers to alter the genome of inheritable “germ” cells and embryos.

The potential of the technology is huge and the theoretical risks like eugenics or cloning are overplayed, argued a panel of the Stem Cell Network.

The step would be a “game-changer,” said Bartha Knoppers, a health-policy expert at McGill University, in a presentation to the annual Till & McCulloch Meetings of stem-cell and regenerative-medicine researchers [These meetings were originally known as the Stem Cell Network’s Annual General Meeting {AGM}]. [emphases mine]

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“I’m completely against any modification of the human genome,” said the unidentified meeting attendee. “If you open this door, you won’t ever be able to close it again.”

If the ban is kept in place, however, Canadian scientists will fall further behind colleagues in other countries, say the experts behind the statement say; they argue possible abuses can be prevented with good ethical oversight.

“It’s a human-reproduction law, it was never meant to ban and slow down and restrict research,” said Vardit Ravitsky, a University of Montreal bioethicist who was part of the panel. “It’s a sort of historical accident … and now our hands are tied.”

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There are fears, as well, that CRISPR could be used to create improved humans who are genetically programmed to have certain facial or other features, or that the editing could have harmful side effects. Regardless, none of it is happening in Canada, good or bad.

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In fact, the Stem Cell Network panel is arguably skirting around the most contentious applications of the technology. It says it is asking the government merely to legalize research for its own sake on embryos and germ cells — those in eggs and sperm — not genetic editing of embryos used to actually get women pregnant.

The highlighted portions in the last two paragraphs of the excerpt were written one year prior to the claims by a Chinese scientist that he had run a clinical trial resulting in gene-edited twins, Lulu and Nana. (See my my November 28, 2018 posting for a comprehensive overview of the original furor). I have yet to publish a followup posting featuring the news that the CRISPR twins may have been ‘improved’ more extensively than originally realized. The initial reports about the twins focused on an illness-related reason (making them HIV ‘immune’) but made no mention of enhanced cognitive skills a side effect of eliminating the gene that would make them HIV ‘immune’. To date, the researcher has not made the bulk of his data available for an in-depth analysis to support his claim that he successfully gene-edited the twins. As well, there were apparently seven other pregnancies coming to term as part of the researcher’s clinical trial and there has been no news about those births.

Risk analysis innovation

Before moving onto the innovation of risk analysis, I want to focus a little more on at least one of the risks that gene-editing might present. Gierczak noted that CRISPR/Cas9 is “not perfect,” which acknowledges the truth but doesn’t convey all that much information.

While the terms ‘precision’ and ‘scissors’ are used frequently when describing the CRISPR technique, scientists actually mean that the technique is significantly ‘more precise’ than other techniques but they are not referencing an engineering level of precision. As for the ‘scissors’, it’s an analogy scientists like to use but in fact CRISPR is not as efficient and precise as a pair of scissors.

Michael Le Page in a July 16, 2018 article for New Scientist lays out some of the issues (Note: A link has been removed),

A study of CRIPSR suggests we shouldn’t rush into trying out CRISPR genome editing inside people’s bodies just yet. The technique can cause big deletions or rearrangements of DNA [emphasis mine], says Allan Bradley of the Wellcome Sanger Institute in the UK, meaning some therapies based on CRISPR may not be quite as safe as we thought.

The CRISPR genome editing technique is revolutionising biology, enabling us to create new varieties of plants and animals and develop treatments for a wide range of diseases.

The CRISPR Cas9 protein works by cutting the DNA of a cell in a specific place. When the cell repairs the damage, a few DNA letters get changed at this spot – an effect that can be exploited to disable genes.

At least, that’s how it is supposed to work. But in studies of mice and human cells, Bradley’s team has found that in around a fifth of cells, CRISPR causes deletions or rearrangements more than 100 DNA letters long. These surprising changes are sometimes thousands of letters long.

…

“I do believe the findings are robust,” says Gaetan Burgio of the Australian National University, an expert on CRISPR who has debunked previous studies questioning the method’s safety. “This is a well-performed study and fairly significant.”

…

I covered the Bradley paper and the concerns in a July 17, 2018 posting ‘The CRISPR ((clustered regularly interspaced short palindromic repeats)-CAS9 gene-editing technique may cause new genetic damage kerfuffle‘. (The ‘kerfufle’ was in reference to a report that the CRISPR market was affected by the publication of Bradley’s paper.)

Despite Health Canada not moving swiftly enough for some researchers, they have nonetheless managed to release an ‘outcome’ report about a consultation/analysis started in October 2016. Before getting to the consultation’s outcome, it’s interesting to look at how the consultation’s call for response was described (from Health Canada’s Toward a strengthened Assisted Human Reproduction Act ; A Consultation with Canadians on Key Policy Proposals webpage),

In October 2016, recognizing the need to strengthen the regulatory framework governing assisted human reproduction in Canada, Health Canada announced its intention to bring into force the dormant sections of the Assisted Human Reproduction Act  and to develop the necessary supporting regulations.

This consultation document provides an overview of the key policy proposals that will help inform the development of regulations to support bringing into force Section 10, Section 12 and Sections 45-58 of the Act. Specifically, the policy proposals describe the Department’s position on the following:

Section 10: Safety of Donor Sperm and Ova

  • Scope and application
  • Regulated parties and their regulatory obligations
  • Processing requirements, including donor suitability assessment
  • Record-keeping and traceability

Section 12: Reimbursement

  • Expenditures that may be reimbursed
  • Process for reimbursement
  • Creation and maintenance of records

Sections 45-58: Administration and Enforcement

  • Scope of the administration and enforcement framework
  • Role of inspectors designated under the Act

The purpose of the document is to provide Canadians with an opportunity to review the policy proposals and to provide feedback [emphasis mine] prior to the Department finalizing policy decisions and developing the regulations. In addition to requesting stakeholders’ general feedback on the policy proposals, the Department is also seeking input on specific questions, which are included throughout the document.

It took me a while to find the relevant section (in particular, take note of ‘Federal Regulatory Oversight’),

3.2. AHR in Canada Today

Today, an increasing number of Canadians are turning to AHR technologies to grow or build their families. A 2012 Canadian studyFootnote 1 found that infertility is on the rise in Canada, with roughly 16% of heterosexual couples experiencing infertility. In addition to rising infertility, the trend of delaying marriage and parenthood, scientific advances in cryopreserving ova, and the increasing use of AHR by LGBTQ2 couples and single parents to build a family are all contributing to an increase in the use of AHR technologies.

The growing use of reproductive technologies by Canadians to help build their families underscores the need to strengthen the AHR Act. While the approach to regulating AHR varies from country to country, Health Canada has considered international best practices and the need for regulatory alignment when developing the proposed policies set out in this document. …

3.2.1 Federal Regulatory Oversight

Although the scope of the AHR Act was significantly reduced in 2012 and some of the remaining sections have not yet been brought into force, there are many important sections of the Act that are currently administered and enforced by Health Canada, as summarized generally below:

…

Section 5: Prohibited Scientific and Research Procedures
Section 5 prohibits certain types of scientific research and clinical procedures that are deemed unacceptable, including: human cloning, the creation of an embryo for non-reproductive purposes, maintaining an embryo outside the human body beyond the fourteenth day, sex selection for non-medical reasons, altering the genome in a way that could be transmitted to descendants, and creating a chimera or a hybrid. [emphasis mine]

….

It almost seems as if the they were hiding the section that broached the human gene-editing question. It doesn’t seem to have worked as it appears, there are some very motivated parties determined to reframe the discussion. Health Canada’s ‘outocme’ report, published March 2019, What we heard: A summary of scanning and consultations on what’s next for health product regulation reflects the success of those efforts,

1.0 Introduction and Context

Scientific and technological advances are accelerating the pace of innovation. These advances are increasingly leading to the development of health products that are better able to predict, define, treat, and even cure human diseases. Globally, many factors are driving regulators to think about how to enable health innovation. To this end, Health Canada has been expanding beyond existing partnerships and engaging both domestically and internationally. This expanding landscape of products and services comes with a range of new challenges and opportunities.

In keeping up to date with emerging technologies and working collaboratively through strategic partnerships, Health Canada seeks to position itself as a regulator at the forefront of health innovation. Following the targeted sectoral review of the Health and Biosciences Sector Regulatory Review consultation by the Treasury Board Secretariat, Health Canada held a number of targeted meetings with a broad range of stakeholders.

This report outlines the methodologies used to look ahead at the emerging health technology environment, [emphasis mine] the potential areas of focus that resulted, and the key findings from consultations.

…

… the Department identified the following key drivers that are expected to shape the future of health innovation:

  1. The use of “big data” to inform decision-making: Health systems are generating more data, and becoming reliant on this data. The increasing accuracy, types, and volume of data available in real time enable automation and machine learning that can forecast activity, behaviour, or trends to support decision-making.
  2. Greater demand for citizen agency: Canadians increasingly want and have access to more information, resources, options, and platforms to manage their own health (e.g., mobile apps, direct-to-consumer services, decentralization of care).
  3. Increased precision and personalization in health care delivery: Diagnostic tools and therapies are increasingly able to target individual patients with customized therapies (e.g., individual gene therapy).
  4. Increased product complexity: Increasingly complex products do not fit well within conventional product classifications and standards (e.g., 3D printing).
  5. Evolving methods for production and distribution: In some cases, manufacturers and supply chains are becoming more distributed, challenging the current framework governing production and distribution of health products.
  6. The ways in which evidence is collected and used are changing: The processes around new drug innovation, research and development, and designing clinical trials are evolving in ways that are more flexible and adaptive.

With these key drivers in mind, the Department selected the following six emerging technologies for further investigation to better understand how the health product space is evolving:

  1. Artificial intelligence, including activities such as machine learning, neural networks, natural language processing, and robotics.
  2. Advanced cell therapies, such as individualized cell therapies tailor-made to address specific patient needs.
  3. Big data, from sources such as sensors, genetic information, and social media that are increasingly used to inform patient and health care practitioner decisions.
  4. 3D printing of health products (e.g., implants, prosthetics, cells, tissues).
  5. New ways of delivering drugs that bring together different product lines and methods (e.g., nano-carriers, implantable devices).
  6. Gene editing, including individualized gene therapies that can assist in preventing and treating certain diseases.

Next, to test the drivers identified and further investigate emerging technologies, the Department consulted key organizations and thought leaders across the country with expertise in health innovation. To this end, Health Canada held seven workshops with over 140 representatives from industry associations, small-to-medium sized enterprises and start-ups, larger multinational companies, investors, researchers, and clinicians in Ottawa, Toronto, Montreal, and Vancouver. [emphases mine]

…

The ‘outocme’ report, ‘What we heard …’, is well worth reading in its entirety; it’s about 9 pp.

I have one comment, ‘stakeholders’ don’t seem to include anyone who isn’t “from industry associations, small-to-medium sized enterprises and start-ups, larger multinational companies, investors, researchers, and clinician” or from “Ottawa, Toronto, Montreal, and Vancouver.” Aren’t the rest of us stakeholders?

Innovating risk analysis

This line in the report caught my eye (from Health Canada’s Toward a strengthened Assisted Human Reproduction Act ; A Consultation with Canadians on Key Policy Proposals webpage),

There is increasing need to enable innovation in a flexible, risk-based way, with appropriate oversight to ensure safety, quality, and efficacy. [emphases mine]

It reminded me of the 2019 federal budget (from my March 22, 2019 posting). One comment before proceeding, regulation and risk are tightly linked and, so, by innovating regulation they are by exttension alos innovating risk analysis,

… Budget 2019 introduces the first three “Regulatory Roadmaps” to specifically address stakeholder issues and irritants in these sectors, informed by over 140 responses [emphasis mine] from businesses and Canadians across the country, as well as recommendations from the Economic Strategy Tables.

Introducing Regulatory Roadmaps

These Roadmaps lay out the Government’s plans to modernize regulatory frameworks, without compromising our strong health, safety, and environmental protections. They contain proposals for legislative and regulatory amendments as well as novel regulatory approaches to accommodate emerging technologies, including the use of regulatory sandboxes and pilot projects—better aligning our regulatory frameworks with industry realities.

Budget 2019 proposes the necessary funding and legislative revisions so that regulatory departments and agencies can move forward on the Roadmaps, including providing the Canadian Food Inspection Agency, Health Canada and Transport Canada with up to $219.1 million over five years, starting in 2019–20, (with $0.5 million in remaining amortization), and $3.1 million per year on an ongoing basis.

In the coming weeks, the Government will be releasing the full Regulatory Roadmaps for each of the reviews, as well as timelines for enacting specific initiatives, which can be grouped in the following three main areas:

What Is a Regulatory Sandbox? Regulatory sandboxes are controlled “safe spaces” in which innovative products, services, business models and delivery mechanisms can be tested without immediately being subject to all of the regulatory requirements.
– European Banking Authority, 2017

…

Establishing a regulatory sandbox for new and innovative medical products
The regulatory approval system has not kept up with new medical technologies and processes. Health Canada proposes to modernize regulations to put in place a regulatory sandbox for new and innovative products, such as tissues developed through 3D printing, artificial intelligence, and gene therapies targeted to specific individuals. [emphasis mine]

Modernizing the regulation of clinical trials
Industry and academics have expressed concerns that regulations related to clinical trials are overly prescriptive and inconsistent. Health Canada proposes to implement a risk-based approach [emphasis mine] to clinical trials to reduce costs to industry and academics by removing unnecessary requirements for low-risk drugs and trials. The regulations will also provide the agri-food industry with the ability to carry out clinical trials within Canada on products such as food for special dietary use and novel foods.

Does the government always get 140 responses from a consultation process? Moving on, I agree with finding new approaches to regulatory processes and oversight and, by extension, new approaches to risk analysis.

Earlier in this post, I asked if someone had a budget for public relations/promotion. I wasn’t joking. My March 22, 2019 posting also included these line items in the proposed 2019 budget,

Budget 2019 proposes to make additional investments in support of the following organizations:
Stem Cell Network: Stem cell research—pioneered by two Canadians in the 1960s [James Till and Ernest McCulloch]—holds great promise for new therapies and medical treatments for respiratory and heart diseases, spinal cord injury, cancer, and many other diseases and disorders. The Stem Cell Network is a national not-for-profit organization that helps translate stem cell research into clinical applications and commercial products. To support this important work and foster Canada’s leadership in stem cell research, Budget 2019 proposes to provide the Stem Cell Network with renewed funding of $18 million over three years, starting in 2019–20.
…
Genome Canada: The insights derived from genomics—the study of the entire genetic information of living things encoded in their DNA and related molecules and proteins—hold the potential for breakthroughs that can improve the lives of Canadians and drive innovation and economic growth. Genome Canada is a not-for-profit organization dedicated to advancing genomics science and technology in order to create economic and social benefits for Canadians. To support Genome Canada’s operations, Budget 2019 proposes to provide Genome Canada with $100.5 million over five years, starting in 2020–21. This investment will also enable Genome Canada to launch new large-scale research competitions and projects, in collaboration with external partners, ensuring that Canada’s research community continues to have access to the resources needed to make transformative scientific breakthroughs and translate these discoveries into real-world applications.
…

Years ago, I managed to find a webpage with all of the proposals various organizations were submitting to a government budget committee. It was eye-opening. You can tell which organizations were able to hire someone who knew the current government buzzwords and the things that a government bureaucrat would want to hear and the organizations that didn’t.

Of course, if the government of the day is adamantly against or uninterested, no amount of persusasion will work to get your organization more money in the budget.

Finally

Reluctantly, I am inclined to explore the topic of emerging technologies such as gene-editing not only in the field of agriculture (for gene-editing of plants, fish, and animals see my November 28, 2018 posting) but also with humans. At the very least, it needs to be discussed whether we choose to participate or not.

If you are interested in the arguments against changing Canada’s prohibition against gene-editing of humans, there’s an Ocotber 2, 2017 posting on Impact Ethics by Françoise Baylis, Professor and Canada Research Chair in Bioethics and Philosophy at Dalhousie University, and Alana Cattapan, Johnson Shoyama Graduate School of Public Policy at the University of Saskatchewan, which makes some compelling arguments. Of course, it was written before the CRISPR twins (my November 28, 2018 posting).

Recaliing CRISPR Therapeutics (mentioned by Gierczak), the company received permission to run clinical trials in the US in October 2018 after the FDA (US Food and Drug Administration) lifted an earlier ban on their trials according to an Oct. 10, 2018 article by Frank Vinhuan for exome,

…

The partners also noted that their therapy is making progress outside of the U.S. They announced that they have received regulatory clearance in “multiple countries” to begin tests of the experimental treatment in both sickle cell disease and beta thalassemia, …

It seems to me that the quotes around “multiple countries” are meant to suggest doubt of some kind. Generally speaking, company representatives make those kinds of generalizations when they’re trying to pump up their copy. E.g., 50% increase in attendance  but no whole numbers to tell you what that means. It could mean two people attended the first year and then brought a friend the next year or 100 people attended and the next year there were 150.

Despite attempts to declare personalized medicine as having arrived, I think everything is still in flux with no preordained outcome. The future has yet to be determined but it will be and I , for one, would like to have some say in the matter.