Category Archives: risk

Five country survey of reactions to food genome editing

Weirdly and even though most of this paper’s authors are from the University of British Columbia (UBC; Canada), only one press release was issued and that was by the lead author’s (Gesa Busch) home institution, the University of Göttingen (Germany).

I’m glad Busch, the other authors, and the work are getting some attention (if not as much as I think they should).

From a July 9, 2021 University of Göttingen press release (also on EurekAlert but published on July 12, 2021),

A research team from the University of Göttingen and the University of British Columbia (Canada) has investigated how people in five different countries react to various usages of genome editing in agriculture. The researchers looked at which uses are accepted and how the risks and benefits of the new breeding technologies are rated by people. The results show only minor differences between the countries studied – Germany, Italy, Canada, Austria and the USA. In all countries, making changes to the genome is more likely to be deemed acceptable when used in crops rather than in livestock. The study was published in Agriculture and Human Values.

Relatively new breeding technologies, such as CRISPR [clustered regularly interspaced short palindromic repeats) gene editing, have enabled a range of new opportunities for plant and animal breeding. In the EU, the technology falls under genetic engineering legislation and is therefore subject to rigorous restrictions. However, the use of gene technologies remains controversial. Between June and November 2019, the research team collected views on this topic via online surveys from around 3,700 people from five countries. Five different applications of gene editing were evaluated: three relate to disease resistance in people, plants, or animals; and two relate to achieving either better quality of produce or a larger quantity of product from cattle.

“We were able to observe that the purpose of the gene modification plays a major role in how it is rated,” says first author Dr Gesa Busch from the University of Göttingen. “If the technology is used to make animals resistant to disease, approval is greater than if the technology is used to increase the output from animals.” Overall, however, the respondents reacted very differently to the uses of the new breeding methods. Four different groups can be identified: strong supporters, supporters, neutrals, and opponents of the technology. The opponents (24 per cent) identify high risks and calls for a ban of the technology, regardless of possible benefits. The strong supporters (21 per cent) see few risks and many advantages. The supporters (26 per cent) see many advantages but also risks. Whereas those who were neutral (29 per cent) show no strong opinion on the subject.

This study was made possible through funding from the Free University of Bozen-Bolzano and Genome BC.

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

Citizen views on genome editing: effects of species and purpose by Gesa Busch, Erin Ryan, Marina A. G. von Keyserlingk & Daniel M. Weary. Agriculture and Human Values (2021) Published: DOI: https://doi.org/10.1007/s10460-021-10235-9

This paper is open access.

Methodology

I have one quick comment about the methodology. It can be difficult to get a sample that breaks down along demographic lines that is close to or identical to national statistics. That said, it was striking to me that every country was under represented in the ’60 years+ ‘ category. In Canada, it was by 10 percentage points (roughly). For other countries the point spread was significantly wider. In Italy, it was a 30 percentage point spread (roughly).

I found the data in the Supplementary Materials yesterday (July 13, 2021). When I looked this morning, that information was no longer there but you will find what appears to be the questionnaire. I wonder if this removal is temporary or permanent and, if permanent, I wonder why it was removed.

Participants for the Canadian portion of the survey were supplied by Dynata, a US-based market research company. Here’s the company’s Wikipedia entry and its website.

Information about how participants were recruited was also missing this morning (July 14, 2021).

Genome British Columbia (Genome BC)

I was a little surprised when I couldn’t find any information about the program or the project on the Genome BC website as the organization is listed as a funder.

There is a ‘Genomics and Society’ tab (seems promising, eh?) on the homepage where you can find the answer to this question: What is GE³LS Research?,

GE3LS research is interdisciplinary, conducted by researchers across many disciplines within social science and humanities, including economics, environment, law, business, communications, and public policy.

There’s also a GE3LS Research in BC page titled Project Search; I had no luck there either.

It all seems a bit mysterious to me and, just in case anything else disappears off the web, here’s a July 13, 2021 news item about the research on phys.org as backup to what I have here.

Health Canada advisory: Face masks that contain graphene may pose health risks

Since COVID-19, we’ve been advised to wear face masks. It seems some of them may not be as safe as we assumed. First, the Health Canada advisory that was issued today, April 2, 2021 and then excerpts from an in-depth posting by Dr. Andrew Maynard (associate dean in the Arizona State University College of Global Futures) about the advisory and the use of graphene in masks.

From the Health Canada Recalls & alerts: Face masks that contain graphene may pose health risks webpage,

Summary

  • Product: Face masks labelled to contain graphene or biomass graphene.
  • Issue: There is a potential that wearers could inhale graphene particles from some masks, which may pose health risks.
  • What to do: Do not use these face masks. Report any health product adverse events or complaints to Health Canada.

Issue

Health Canada is advising Canadians not to use face masks that contain graphene because there is a potential that they could inhale graphene particles, which may pose health risks.

Graphene is a novel nanomaterial (materials made of tiny particles) reported to have antiviral and antibacterial properties. Health Canada conducted a preliminary scientific assessment after being made aware that masks containing graphene have been sold with COVID-19 claims and used by adults and children in schools and daycares. Health Canada believes they may also have been distributed for use in health care settings.

Health Canada’s preliminary assessment of available research identified that inhaled graphene particles had some potential to cause early lung toxicity in animals. However, the potential for people to inhale graphene particles from face masks and the related health risks are not yet known, and may vary based on mask design. The health risk to people of any age is not clear. Variables, such as the amount and duration of exposure, and the type and characteristics of the graphene material used, all affect the potential to inhale particles and the associated health risks. Health Canada has requested data from mask manufacturers to assess the potential health risks related to their masks that contain graphene.

Until the Department completes a thorough scientific assessment and has established the safety and effectiveness of graphene-containing face masks, it is taking the precautionary approach of removing them from the market while continuing to gather and assess information. Health Canada has directed all known distributors, importers and manufacturers to stop selling and to recall the affected products. Additionally, Health Canada has written to provinces and territories advising them to stop distribution and use of masks containing graphene. The Department will continue to take appropriate action to stop the import and sale of graphene face masks.

Products affected

Face masks labelled as containing graphene or biomass graphene.

What you should do

  • Do not use face masks labelled to contain graphene or biomass graphene.
  • Consult your health care provider if you have used graphene face masks and have health concerns, such as new or unexplained shortness of breath, discomfort or difficulty breathing.
  • Report any health product adverse events or complaints regarding graphene face masks to Health Canada.

Dr. Andrew Maynard’s Edge of Innovation series features a March 26, 2021 posting about the use of graphene in masks (Note: Links have been removed),

Face masks should protect you, not place you in greater danger. However, last Friday Radio Canada revealed that residents of Quebec and Ottawa were being advised not to use specific types of graphene-containing masks as they could potentially be harmful.

The offending material in the masks is graphene — a form of carbon that consists of nanoscopically thin flakes of hexagonally-arranged carbon atoms. It’s a material that has a number of potentially beneficial properties, including the ability to kill bacteria and viruses when they’re exposed to it.

Yet despite its many potential uses, the scientific jury is still out when it comes to how safe the material is.

As with all materials, the potential health risks associated with graphene depend on whether it can get into the body, where it goes if it can, what it does when it gets there, and how much of it is needed to cause enough damage to be of concern.

Unfortunately, even though these are pretty basic questions, there aren’t many answers forthcoming when it comes to the substance’s use in face masks.

Early concerns around graphene were sparked by previous research on another form of carbon — carbon nanotubes. It turns out that some forms of these fiber-like materials can cause serious harm if inhaled. And following on from research here, a natural next-question to ask is whether carbon nanotubes’ close cousin graphene comes with similar concerns.

Because graphene lacks many of the physical and chemical aspects of carbon nanotubes that make them harmful (such as being long, thin, and hard for the body to get rid of), the indications are that the material is safer than its nanotube cousins. But safer doesn’t mean safe. And current research indicates that this is not a material that should be used where it could potentially be inhaled, without a good amount of safety testing first.

[downloaded from https://medium.com/edge-of-innovation/how-safe-are-graphene-based-face-masks-b88740547e8c] Original source: Wikimedia

When it comes to inhaling graphene, the current state of the science indicates that if the material can get into the lower parts of the lungs (the respirable or alveolar region) it can lead to an inflammatory response at high enough concentrations.

There is some evidence that adverse responses are relatively short-lived, and that graphene particles can be broken down and disposed of by the lungs’ defenses.

This is good news as it means that there are less likely to be long-term health impacts from inhaling the material.

There’s also evidence that graphene, unlike some forms of thin, straight carbon nanotubes, does not migrate to the outside layers of the lungs where it could potentially do a lot more damage.

Again, this is encouraging as it suggests that graphene is unlikely to lead to serious long-term health impacts like mesothelioma.

However, research also shows that this is not a benign material. Despite being made of carbon — and it’s tempting to think of carbon as being safe, just because we’re familiar with it — there is some evidence that the jagged edges of some graphene particles can harm cells, leading to local damage as the body responds to any damage the material causes.

There are also concerns, although they are less well explored in the literature, that some forms of graphene may be carriers for nanometer-sized metal particles that can be quite destructive in the lungs. This is certainly the case with some carbon nanotubes, as the metallic catalyst particles used to manufacture them become embedded in the material, and contribute to its toxicity.

The long and short of this is that, while there are still plenty of gaps in our knowledge around how much graphene it’s safe to inhale, inhaling small graphene particles probably isn’t a great idea unless there’s been comprehensive testing to show otherwise.

And this brings us to graphene-containing face masks.

….

Here, it’s important to stress that we don’t yet know if graphene particles are being released and, if they are, whether they are being released in sufficient quantities to cause health effects. And there are indications that, if there are health risks, these may be relatively short-term — simply because graphene particles may be effectively degraded by the lungs’ defenses.

At the same time, it seems highly irresponsible to include a material with unknown inhalation risks in a product that is intimately associated with inhalation. Especially when there are a growing number of face masks available that claim to use graphene.

… There are millions of graphene face masks and respirators being sold and used around the world. And while the unfolding news focuses on Quebec and one particular type of face mask, this is casting uncertainty over the safety of any graphene-containing masks that are being sold.

And this uncertainty will persist until manufacturers and regulators provide data indicating that they have tested the products for the release and subsequent inhalation of fine graphene particles, and shown the risks to be negligible.

I strongly recommend reading, in its entirety , Dr. Maynard’s March 26, 2021 posting, Which he has updated twice since first posting the story.

In short. you may want to hold off before buying a mask with graphene until there’s more data about safety.

Could synergistic action of engineered nanoparticles have a health impact?

Synergistic action can be difficult to study especially when you’re looking at nanoparticles which could be naturally occurring and/or engineered. I believe this study is focused on engineered nanoparticles (ENPs) and I think it’s the first one I’ve seen that examines synergistic action of any kind. So, bravo to the scientists for tackling a very ambitious project.

An October 1, 2020 news item on phys.org describes this work from Denmark,

Nanoparticles are used in a wide range of products and manufacturing processes because the properties of a material can change dramatically when the material comes in nano-form.

They can be used, for example, to purify wastewater and to transport medicine around the body. They are also added to, for example, socks, pillows, mattresses, phone covers and refrigerators to supply the items with an antibacterial surface.

Much research has been done on how nanoparticles affect humans and the environment and a number of studies have shown that nanoparticles can disrupt or damage our cells.

This is confirmed by a new study that has also looked at how cells react when exposed to more than one kind of nano particle at the same time.

An October 1, 2020 University of Southern Denmark press release (also on EurekAlert) by Birgitte Svennevig, which originated the news item, provides more insight into the research,

The lead author of the study is Barbara Korzeniowska from the Department of Biochemistry and Molecular Biology at SDU. The head of research is Professor Frank Kjeldsen from the same department.

His research into metal nanoparticles is supported by a European Research Grant of DKK 14 million.

“Throughout a lifetime, we are exposed to many different kinds of nano-particles, and we should investigate how the combination of different nano-particles affects us and also whether an accumulation through life can harm us,” says Barbara Korzeniowska.

She herself became interested in the subject when her little daughter one day was going in the bathtub and got a rubber duck as a toy.

– It turned out that it had been treated with nano-silver, probably to keep it free of bacteria, but small children put their toys in their mouths, and she could thus ingest nano-silver. That is highly worrying when research shows that nano-silver can damage human cells, she says.

In her new study, she looked at nano-silver and nano-platinum. She has investigated their individual effect and whether exposure of both types of nanoparticles results in a synergy effect in two types of brain cells.

– There are almost no studies of the synergy effect of nano particles, so it is important to get started with these studies, she says.

She chose nano-silver because it is already known to be able to damage cells and nano-platinum, because nano-platinum is considered to be so-called bio-inert; i.e. has a minimal interaction with human tissue.

The nanoparticles were tested on two types of brain cells: astrocytes and endothelial cells. Astrocytes are supporter cells in the central nervous system, which i.a. helps to supply the nervous system with nutrients and repair damage to the brain. Endothelial cells sit on the inside of the blood vessels and transport substances from the bloodstream to the brain.

When the endothelial cells were exposed to nano-platinum, nothing happened. When exposed to nano-silver, their ability to divide deteriorated. When exposed to both nano-silver and nano-platinum, the effect was amplified, and they died in large numbers. Furthermore, their defense mechanisms decreased, and they had difficulty communicating with each other.

– So even though nano-platinum alone does not do harm, something drastic happens when they are combined with a different kind of nano-particle, says Frank Kjeldsen.

The astrocytes were more hardy and reacted “only” with impaired ability to divide when exposed to both types of nano-particles.

An earlier study, conducted by Frank Kjeldsen, has shown a dramatic synergy effect of silver nanoparticles and cadmium ions, which are found naturally all around us on Earth.

In that study, 72 % of the cells died (in this study it was intestinal cells) as they were exposed to both nano-silver and cadmium ions. When they were only exposed to nano-silver, 25% died. When exposed to cadmium ions only, 12% died.

We are involuntarily exposed

– Little is known about how large concentrations of nano-particles are used in industrial products. We also do not know what size particles they use – size also has an effect on whether they can enter a cell, says Barbara Korzeniowska and continues:

– But we know that a lot of people are involuntarily exposed to nano-particles, and that there can be lifelong exposure.

There are virtually no restrictions on adding nanoparticles to products. In the EU, however, manufacturers must have an approval if they want to use nanoparticles in products with antibacterial properties. In Denmark, they must also declare nano-content in such products on the label.

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

The Cytotoxicity of Metal Nanoparticles Depends on Their Synergistic Interactions by Barbara Korzeniowska, Micaella P. Fonseca, Vladimir Gorshkov, Lilian Skytte, Kaare L. Rasmussen, Henrik D. Schrøder, Frank Kjeldsen. Particle Volume 37, Issue 8, August 2020,. 2000135 DOI: https://doi.org/10.1002/ppsc.202000135 First published: 06 July 2020

This paper is behind a paywall.

Food sensor made from of silk microneedles looks like velco

These sensors really do look like velcro,

The Velcro-like food sensor, made from an array of silk microneedles, can pierce through plastic packaging to sample food for signs of spoilage and bacterial contamination. Image: Felice Frankel

A September 9, 2020 news item on Nanowerk announces some research from the Massachusetts Institute (MIT),

MIT engineers have designed a Velcro-like food sensor, made from an array of silk microneedles, that pierces through plastic packaging to sample food for signs of spoilage and bacterial contamination.

The sensor’s microneedles are molded from a solution of edible proteins found in silk cocoons, and are designed to draw fluid into the back of the sensor, which is printed with two types of specialized ink. One of these “bioinks” changes color when in contact with fluid of a certain pH range, indicating that the food has spoiled; the other turns color when it senses contaminating bacteria such as pathogenic E. coli.

A Sept. 9, 2020 MIT news release (also on EurekAlert), which originated the news item, delves further into the research,

The researchers attached the sensor to a fillet of raw fish that they had injected with a solution contaminated with E. coli. After less than a day, they found that the part of the sensor that was printed with bacteria-sensing bioink turned from blue to red — a clear sign that the fish was contaminated. After a few more hours, the pH-sensitive bioink also changed color, signaling that the fish had also spoiled.

The results, published today in the journal Advanced Functional Materials, are a first step toward developing a new colorimetric sensor that can detect signs of food spoilage and contamination.

Such smart food sensors might help head off outbreaks such as the recent salmonella contamination in onions and peaches. They could also prevent consumers from throwing out food that may be past a printed expiration date, but is in fact still consumable.

“There is a lot of food that’s wasted due to lack of proper labeling, and we’re throwing food away without even knowing if it’s spoiled or not,” says Benedetto Marelli, the Paul M. Cook Career Development Assistant Professor in MIT’s Department of Civil and Environmental Engineering. “People also waste a lot of food after outbreaks, because they’re not sure if the food is actually contaminated or not. A technology like this would give confidence to the end user to not waste food.”

Marelli’s co-authors on the paper are Doyoon Kim, Yunteng Cao, Dhanushkodi Mariappan, Michael S. Bono Jr., and A. John Hart.

Silk and printing

The new food sensor is the product of a collaboration between Marelli, whose lab harnesses the properties of silk to develop new technologies, and Hart, whose group develops new manufacturing processes.

Hart recently developed a high-resolution floxography technique, realizing microscopic patterns that can enable low-cost printed electronics and sensors. Meanwhile, Marelli had developed a silk-based microneedle stamp that penetrates and delivers nutrients to plants. In conversation, the researchers wondered whether their technologies could be paired to produce a printed food sensor that monitors food safety.

“Assessing the health of food by just measuring its surface is often not good enough. At some point, Benedetto mentioned his group’s microneedle work with plants, and we realized that we could combine our expertise to make a more effective sensor,” Hart recalls.

The team looked to create a sensor that could pierce through the surface of many types of food. The design they came up with consisted of an array of microneedles made from silk.

“Silk is completely edible, nontoxic, and can be used as a food ingredient, and it’s mechanically robust enough to penetrate through a large spectrum of tissue types, like meat, peaches, and lettuce,” Marelli says.

A deeper detection

To make the new sensor, Kim first made a solution of silk fibroin, a protein extracted from moth cocoons, and poured the solution into a silicone microneedle mold. After drying, he peeled away the resulting array of microneedles, each measuring about 1.6 millimeters long and 600 microns wide — about one-third the diameter of a spaghetti strand.

The team then developed solutions for two kinds of bioink — color-changing printable polymers that can be mixed with other sensing ingredients. In this case, the researchers mixed into one bioink an antibody that is sensitive to a molecule in E. coli. When the antibody comes in contact with that molecule, it changes shape and physically pushes on the surrounding polymer, which in turn changes the way the bioink absorbs light. In this way, the bioink can change color when it senses contaminating bacteria.

The researchers made a bioink containing antibodies sensitive to E. coli, and a second bioink sensitive to pH levels that are associated with spoilage. They printed the bacteria-sensing bioink on the surface of the microneedle array, in the pattern of the letter “E,” next to which they printed the pH-sensitive bioink, as a “C.” Both letters initially appeared blue in color.

Kim then embedded pores within each microneedle to increase the array’s ability to draw up fluid via capillary action. To test the new sensor, he bought several fillets of raw fish from a local grocery store and injected each fillet with a fluid containing either E. coli, Salmonella, or the fluid without any contaminants. He stuck a sensor into each fillet. Then, he waited.

After about 16 hours, the team observed that the “E” turned from blue to red, only in the fillet contaminated with E. coli, indicating that the sensor accurately detected the bacterial antigens. After several more hours, both the “C” and “E” in all samples turned red, indicating that every fillet had spoiled.

The researchers also found their new sensor indicates contamination and spoilage faster than existing sensors that only detect pathogens on the surface of foods.

“There are many cavities and holes in food where pathogens are embedded, and surface sensors cannot detect these,” Kim says. “So we have to plug in a bit deeper to improve the reliability of the detection. Using this piercing technique, we also don’t have to open a package to inspect food quality.”

The team is looking for ways to speed up the microneedles’ absorption of fluid, as well as the bioinks’ sensing of contaminants. Once the design is optimized, they envision the sensor could be used at various stages along the supply chain, from operators in processing plants, who can use the sensors to monitor products before they are shipped out, to consumers who may choose to apply the sensors on certain foods to make sure they are safe to eat.

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

A Microneedle Technology for Sampling and Sensing Bacteria in the Food Supply Chain by Doyoon Kim, Yunteng Cao, Dhanushkodi Mariappan, Michael S. Bono Jr., A. John Hart, Benedetto Marelli. DOI: https://doi.org/10.1002/adfm.202005370 First published: 09 September 2020

This paper is behind a paywall.

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

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.

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),

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

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

Which abilities are seen as more important than others?

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

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

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

Ethics of clinical trials for testing brain implants

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.

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

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

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

Brain-computer interfaces, symbiosis, and ethical issues

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

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.”

###

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

###

About the Study

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

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

About the Gladstone Institute

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

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

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

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

This paper is behind a paywall.

Money

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

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

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

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

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

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

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

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

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

Anand Giridharadas‏Verified account @AnandWrites



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

7:34 PM – 8 Jul 2019

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

AstraZeneca

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

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

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

Controversies

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

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

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

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

Innovative Genomics Institute (IGI)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Gladstone Institutes

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Final comments

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

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

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

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.