Tag Archives: CRISPR/Cas9

The CRISPR ((clustered regularly interspaced short palindromic repeats)-CAS9 gene-editing technique may cause new genetic damage kerfuffle

Setting the stage

Not unexpectedly, CRISPR-Cas9  or clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 can be dangerous as these scientists note in a July 16, 2018 news item on phys.org,

Scientists at the Wellcome Sanger Institute have discovered that CRISPR/Cas9 gene editing can cause greater genetic damage in cells than was previously thought. These results create safety implications for gene therapies using CRISPR/Cas9 in the future as the unexpected damage could lead to dangerous changes in some cells.

Reported today (16 July 2018) in the journal Nature Biotechnology, the study also revealed that standard tests for detecting DNA changes miss finding this genetic damage, and that caution and specific testing will be required for any potential gene therapies.

This CRISPR-Cas9 image reminds me of popcorn,

CRISPR-associated protein Cas9 (white) from Staphylococcus aureus based on Protein Database ID 5AXW. Credit: Thomas Splettstoesser (Wikipedia, CC BY-SA 4.0)[ downloaded from https://phys.org/news/2018-07-genome-crisprcas9-gene-higher-thought.html#jCp]

A July 16, 2018 Wellcome Sanger Institute press release (also on EurekAlert), which originated the news item, offers a little more explanation,

CRISPR/Cas9 is one of the newest genome editing tools. It can alter sections of DNA in cells by cutting at specific points and introducing changes at that location. Already extensively used in scientific research, CRISPR/Cas9 has also been seen as a promising way to create potential genome editing treatments for diseases such as HIV, cancer or sickle cell disease. Such therapeutics could inactivate a disease-causing gene, or correct a genetic mutation. However, any potential treatments would have to prove that they were safe.

Previous research had not shown many unforeseen mutations from CRISPR/Cas9 in the DNA at the genome editing target site. To investigate this further the researchers carried out a full systematic study in both mouse and human cells and discovered that CRISPR/Cas9 frequently caused extensive mutations, but at a greater distance from the target site.

The researchers found many of the cells had large genetic rearrangements such as DNA deletions and insertions. These could lead to important genes being switched on or off, which could have major implications for CRISPR/Cas9 use in therapies. In addition, some of these changes were too far away from the target site to be seen with standard genotyping methods.

Prof Allan Bradley, corresponding author on the study from the Wellcome Sanger Institute, said: “This is the first systematic assessment of unexpected events resulting from CRISPR/Cas9 editing in therapeutically relevant cells, and we found that changes in the DNA have been seriously underestimated before now. It is important that anyone thinking of using this technology for gene therapy proceeds with caution, and looks very carefully to check for possible harmful effects.”

Michael Kosicki, the first author from the Wellcome Sanger Institute, said: “My initial experiment used CRISPR/Cas9 as a tool to study gene activity, however it became clear that something unexpected was happening. Once we realised the extent of the genetic rearrangements we studied it systematically, looking at different genes and different therapeutically relevant cell lines, and showed that the CRISPR/Cas9 effects held true.”

The work has implications for how CRISPR/Cas9 is used therapeutically and is likely to re-spark researchers’ interest in finding alternatives to the standard CRISPR/Cas9 method for gene editing.

Prof Maria Jasin, an independent researcher from Memorial Slone Kettering Cancer Centre, New York, who was not involved in the study said: “This study is the first to assess the repertoire of genomic damage arising at a CRISPR/Cas9 cleavage site. While it is not known if genomic sites in other cell lines will be affected in the same way, this study shows that further research and specific testing is needed before CRISPR/Cas9 is used clinically.”

For anyone who’d like to better understand the terms gene editing and CRISPR-Cas9, the Wellcome Sanger Institute provides these explanatory webpages, What is genome editing? and What is CRISPR-Cas9?

For the more advanced, here’s a link and a citation for the paper,

Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements by Michael Kosicki, Kärt Tomberg, & Allan Bradley. Nature Biotechnology DOI: https://doi.org/10.1038/nbt.4192 Published 16 July 2018

This paper appears to be open access.

The kerfuffle

It seems this news has affected the CRISPR market. From a July 16, 2018 article by Cale Guthrie Weissman for Fast Company,

… CRISPR could unknowingly delete or alter non-targeted genes, which could lead to myriad unintended consequences. This is especially frightening, since the technology is going to be used in human clinical trials.

Meanwhile, other scientists working with CRISPR are trying to downplay the findings, telling STAT [a life sciences and business journalism website] that there have been no reported adverse effects similar to what the study describes. The news, however, has brought about a market reaction–at least three publicly traded companies that focus on CRISPR-based therapies are in stock nosedive. Crispr Therapeutics is down by over 6%; Editas fell by over 3%; and Intellia Therapeutics dropped by over 5%. [emphasis mine]

Damage control

Gaetan Burgio (geneticist, Australian National University)  in a July 16, 2018 essay on phys.org (originating from The Conversation) suggests some calm (Note: Links have been removed),

But a new study has called into question the precision of the technique [CRISPR gene editing technology].

The hope for gene editing is that it will be able to cure and correct diseases. To date, many successes have been reported, including curing deafness in mice, and in altering cells to cure cancer.

Some 17 clinical trials in human patients are registered [emphasis mine] testing gene editing on leukaemias, brain cancers and sickle cell anaemia (where red blood cells are misshaped, causing them to die). Before implementing CRISPR technology in clinics to treat cancer or congenital disorders, we must address whether the technique is safe and accurate.

There are a few options for getting around this problem. One option is to isolate the cells we wish to edit from the body and reinject only the ones we know have been correctly edited.

For example, lymphocytes (white blood cells) that are crucial to killing cancer cells could be taken out of the body, then modified using CRISPR to heighten their cancer-killing properties. The DNA of these cells could be sequenced in detail, and only the cells accurately and specifically gene-modified would be selected and delivered back into the body to kill the cancer cells.

While this strategy is valid for cells we can isolate from the body, some cells, such as neurons and muscles, cannot be removed from the body. These types of cells might not be suitable for gene editing using Cas9 scissors.

Fortunately, researchers have discovered other forms of CRISPR systems that don’t require the DNA to be cut. Some CRISPR systems only cut the RNA, not the DNA (DNA contains genetic instructions, RNA convey the instructions on how to synthesise proteins).

As RNA [ribonucleic acid] remains in our cells only for a specific period of time before being degraded, this would allow us to control the timing and duration of the CRISPR system delivery and reverse it (so the scissors are only functional for a short period of time).

This was found to be successful for dementia in mice. Similarly, some CRISPR systems simply change the letters of the DNA, rather than cutting them. This was successful for specific mutations causing diseases such as hereditary deafness in mice.

I agree with Burgio’s conclusion (not included here) that we have a lot more to learn and I can’t help wondering why there are 17 registered human clinical trials at this point.

Nanoparticle-based delivery platform for CRISPR-Cas9 (gene-editing technology)

A February 18, 2018 King Abdullah University of Science and Technology (KAUST; Saudi Arabia) news release (also on EurekAlert but published on Feb. 20, 2018) describes a new technology for delivering CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 into cells,

A new delivery system for introducing gene-editing technology into cells could help safely and efficiently correct disease-causing mutations in patients.

The system, developed by KAUST scientists, is the first to use sponge-like ensembles of metal ions and organic molecules to coat the molecular components of the precision DNA-editing technology known as CRISPR/Cas9, allowing efficient release of the genome-editing machinery inside the cell.

“This method presents an easy and economically feasible route to improve on the delivery problems that accompany RNA-based therapeutic approaches,” says Niveen Khashab, the associate professor of chemical sciences at KAUST who led the study. “This may permit such formulations to be eventually used for treating genetic diseases effectively in the future.”

CRISPR/Cas9 has a double delivery problem: For the gene-editing technology to work like a molecular Swiss Army knife, both a large protein (the Cas9 cutting enzyme) and a highly charged RNA component (the guide RNA used for DNA targeting) must each get from the outside of the cell into the cytoplasm and finally into the nucleus, all without getting trapped in the tiny intracellular bubbles that are known as endosomes.

To solve this problem, Khashab and her lab turned to a nano-sized type of porous material known as a zeolitic imidazolate framework, which forms a cage-like structure into which other molecules can be placed. The researchers encapsulated the Cas9 protein and guide RNA in this material and then introduced the resulting nanoparticles into hamster cells.

The encapsulated CRISPR-Cas9 constructs were not toxic to the cells. And because particles in the coating material become positively charged when absorbed into endosomes, they caused these membrane-bound bubbles to burst, freeing the CRISPR-Cas9 machinery to travel to the nucleus, home to the cell’s genome. There the gene-editing technology could get to work.

Using a guide RNA designed to target a gene that caused the cells to glow green under fluorescent light, Khashab and her team showed that they could reduce the expression of this gene by 37 percent over four days with their technology. “These cage-like structures are biocompatible and can be triggered on demand, making them smart options to overcome delivery problems of genetic materials and proteins,” says the study’s first author Shahad Alsaiari, a Ph.D. student in Khashab’s lab.

The researchers’ plan to test their system in human cells and in mice, and eventually, they hope, in clinical trials.

The zeolitic imidazolate framework forms a cage-like scaffold over the CRISPR/Cas9 machinery.. Reprinted (adapted) with permission from Alsaiari, S.K., Patil, S., Alyami, M., Alamoudi, K.O., Aleisa, F.A., Merzaban, J., Li M. & Khashab, N.M. Endosomal escape and delivery of CRISPR/Cas9 genome editing machinery enabled by nanoscale zeolitic imidazolate framework. Journal of the American Chemical Society 140, 143–146 (2018). © 2018 American Chemical Society; KAUST Xavier Pita and Heno Huang ][downloaded from https://discovery.kaust.edu.sa/en/article/475/a%250adelivery-platform-for-gene-editing-technology]

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

Endosomal Escape and Delivery of CRISPR/Cas9 Genome Editing Machinery Enabled by Nanoscale Zeolitic Imidazolate Framework by Shahad K. Alsaiari, Sachin Patil, Mram Alyami, Kholod O. Alamoudi, Fajr A. Aleisa, Jasmeen S. Merzaban, Mo Li, and Niveen M. Khashab. J. Am. Chem. Soc., 2018, 140 (1), pp 143–146 DOI: 10.1021/jacs.7b11754 Publication Date (Web): December 22, 2017

Copyright © 2017 American Chemical Society

This paper is behind a paywall.

Acoustic nanomotors deliver Cas9-sgRNA complex to the cell

The gene editing tool .CRISPR (clustered regularly interspaced short palindromic repeats) does feature in this story but only as a minor character; the real focus is on the delivery system. From a February 9, 2018 news item on Nanowerk ()Note: A link has been removed),

In cancer research, the “Cas-9–sgRNA” complex is an effective genomic editing tool, but its delivery across the cell membrane to the target (tumor) genome has not yet been satisfactorily solved.

American and Danish scientists have now developed an active nanomotor for the efficient transport, delivery, and release of this gene scissoring system. As detailed in their paper in the journal Angewandte Chemie (“Active Intracellular Delivery of a Cas9/sgRNA Complex Using Ultrasound-Propelled Nanomotors”), their nanovehicle is propelled towards its target by ultrasound.

The publisher (Wiley) has made this image illustrating the work available,

Courtesy: Wiley

A February 9, 2018 Wiley Publications news release (also on EurekAlert), which originated the news item, provides more information,

Genomic engineering as a promising cancer therapeutic approach has experienced a tremendous surge since the discovery of the adaptive bacterial immune defense system “CRISPR” and its potential as a gene editing tool over a decade ago. Engineered CRISPR systems for gene editing now contain two main components, a single guide RNA or sgRNA and Cas-9 nuclease. While the sgRNA guides the nuclease to the specified gene sequence, Cas-9 nuclease performs its editing with surgical efficiency. However, the delivery of the large machinery to the target genome is still problematic. The authors of the Angewandte Chemie study, Liangfang Zhang and Joseph Wang from the University of California San Diego, and their colleagues now propose ultrasound-propelled gold nanowires as an active transport/release vehicle for the Cas9-sgRNA complex over the membrane.

Gold nanowires may cross a membrane passively, but thanks to their rod- or wirelike asymmetric shape, active motion can be triggered by ultrasound. “The asymmetric shape of the gold nanowire motor, given by the fabrication process, is essential for the acoustic propulsion,” the authors remarked. They assembled the vehicle by attaching the Cas-9 protein/RNA complex to the gold nanowire through sulfide bridges. These reduceable linkages have the advantage that inside the tumor cell, the bonds would be broken by glutathione, a natural reducing compound enriched in tumor cells. The Cas9-sgRNA would be released and sent to the nucleus to do its editing work, for, example, the knockout of a gene.

As a test system, the scientists monitored the suppression of fluorescence emitted by green fluorescence protein expressing melanoma B16F10 cells. Ultrasound was applied for five minutes, which accelerated the nanomotor carrying the Cas9-sgRNA complex across the membrane, accelerating it even inside the cell, as the authors noted. Moreover, they observed their Cas9-sgRNA complex effectively suppressing fluorescence with only tiny concentrations of the complex needed.

Thus, both the effective use of an acoustic nanomotor as an active transporter and the small payload needed for efficient gene knockout are intriguing results of the study. The simplicity of the system, which uses only few and readily available components, is another remarkable achievement.

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

Active Intracellular Delivery of a Cas9/sgRNA Complex Using Ultrasound-Propelled Nanomotors by Malthe Hansen-Bruhn, Dr. Berta Esteban-Fernández de Ávila, Dr. Mara Beltrán-Gastélum, Prof. Jing Zhao, Dr. Doris E. Ramírez-Herrera, Pavimol Angsantikul, Prof. Kurt Vesterager Gothelf, Prof. Liangfang Zhang, and Prof. Joseph Wang. Angewandte Chemie International Edition Vol. 57 Issue 7 DOI: 10.1002/anie.201713082 Version of Record online: 6 FEB 2018

© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

Immune to CRISPR?

I guess if you’re going to use bacteria as part of your gene editing technology (CRISPR [clustered regularly interspaced short palindromic repeats]/Cas9) then, you might half expect the body’s immune system may have developed some defenses. A Jan. 9, 2018 article by Sarah Zhang for The Atlantic provides some insight into what the new research suggests (Note: Links have been removed),

2018 is supposed to be the year of CRISPR in humans. The first U.S. and European clinical trials that test the gene-editing tool’s ability to treat diseases—such as sickle-cell anemia, beta thalassemia, and a type of inherited blindness—are slated to begin this year.

But the year has begun on a cautionary note. On Friday [January 5, 2018], Stanford researchers posted a preprint (which has not been peer reviewed) to the website biorXiv highlighting a potential obstacle to using CRISPR in humans: Many of us may already be immune to it. That’s because CRISPR actually comes from bacteria that often live on or infect humans, and we have built up immunity to the proteins from these bacteria over our lives.

Not all CRISPR therapies in humans will be doomed. “We don’t think this is the end of the story. This is the start of the story,” says Porteus [Matthew Porteus, a pediatrician and stem-cell researcher at Stanford]. There are likely ways around the problem of immunity to CRISPR proteins, and many of the early clinical trials appear to be designed around this problem.

Porteus and his colleagues focused on two versions of Cas9, the bacterial protein mostly commonly used in CRISPR gene editing. One comes from Staphylococcus aureus, which often harmlessly lives on skin but can sometimes causes staph infections, and another from Streptococcus pyogenes, which causes strep throat but can also become “flesh-eating bacteria” when it spreads to other parts of the body. So yeah, you want your immune system to be on guard against these bacteria.

The human immune system has a couple different ways of recognizing foreign proteins, and the team tested for both. First, they looked to see if people have molecules in their blood called antibodies that can specifically bind to Cas9. Among 34 people they tested, 79 percent had antibodies against the staph Cas9 and 65 percent against the strep Cas9.

The Stanford team only tested for preexisting immunity against Cas9, but anytime you inject a large bacterial protein into the human body, it can provoke an immune response. After all, that’s how the immune system learns to fight off bacteria it’s never seen before. (Preexisting immunity can make the response faster and more robust, though.)

The danger of the immune system turning on a patient’s body hangs over a lot of research into correcting genes. In the late 1990s and 2000s, research into gene therapy was derailed by the death of 18-year-old Jesse Gelsinger, who died from an immune reaction to the virus used to deliver the corrected gene. This is the worst-case scenario that the CRISPR world hopes to avoid.

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

Identification of Pre-Existing Adaptive Immunity to Cas9 Proteins in Humans by Carsten Trevor Charlesworth, Priyanka S Deshpande, Daniel P Dever, Beruh Dejene, Natalia Gomez-Ospina, Sruthi Mantri, Mara Pavel-Dinu, Joab Camarena, Kenneth I Weinberg, Matthew H Porteus. bioRxiv posted January 5, 2018 doi: https://doi.org/10.1101/243345

This article is a preprint and has not been peer-reviewed …

This preprint (not yet published paper) is open access and open for feedback.

Meanwhile, the year of CRISPR takes off (from a January 10, 2018 American Chemical Society news release on EurekAlert),

This year could be a defining one for CRISPR, the gene editing technique, which has been hailed as an important breakthrough in laboratory research. That’s because the first company-sponsored clinical studies will be conducted to see if it can help treat diseases in humans, according to an article in Chemical & Engineering News (C&EN), the weekly newsmagazine of the American Chemical Society.

C&EN Assistant Editor Ryan Cross reports that a big push is coming from industry, specifically from three companies that are each partly founded by one of the three inventors of the method. They are zeroing in on the blood diseases called sickle-cell anemia and β-thalassemia, mostly because their precise cause is known. In these diseases, hemoglobin doesn’t function properly, leading to severe health issues in some people. Crispr Therapeutics and Intellia Therapeutics plan to test the technique to boost levels of an alternative version of healthy hemoglobin. Editas Medicine, however, will also use CRISPR to correct mutations in the faulty hemoglobin gene. Labs led by university researchers are also joining the mix, starting or continuing clinical trials with the approach in 2018.

Because CRISPR is being used to cut a cell’s DNA and insert a new sequence, concerns have been raised about the potential for accidents. A cut in the wrong place could mean introducing a new mutation that could be benign — or cancerous. But according to proponents of the method, researchers are conducting extensive computer predictions and in vitro tests to help avoid this outcome.

The January 8, 2018 Chemical and Engineering News (C&EN) open access article by Ryan Cross is here.

Finally, if you are interested in how this affects research as it’s being developed, there’s University of British Columbia researcher Rosie Redfield’s January 16, 2018 posting on RRResearch blog,

Thursday’s [January 11, 2018] post described the hypothesis that bacteria might use gene transfer agent particles to inoculate other cells in the population with fragments of phage DNA, and outlined an experiment to test this.  Now I’m realizing that I need to know a lot more about the kind of immunity I should expect to see if this GTA-as-vaccine hypothesis is correct.

That should give you some idea of what I meant by “research as it’s being developed.” Redfield’s blog is not for the mildly interested.

Redfield is well-known internationally as being one of the first to refute research which suggested the existence of an ‘arsenic bacterium’ (see my Dec. 8, 2010 posting: My apologies for arsenic blooper. She’s first mentioned in the second excerpt, second paragraph.) The affair was known online as #arseniclife. There’s a May 27, 2011 essay by Carl Zimmer on Slate titled: The Discovery of Arsenic-Based Twitter: How #arseniclife changed science.

A transatlantic report highlighting the risks and opportunities associated with synthetic biology and bioengineering

I love e-Life, the open access journal where its editors noted that a submitted synthetic biology and bioengineering report was replete with US and UK experts (along with a European or two) but no expert input from other parts of the world. In response the authors added ‘transatlantic’ to the title. It was a good decision since it was too late to add any new experts if the authors planned to have their paper published in the foreseeable future.

I’ve commented many times here when panels of experts include only Canadian, US, UK, and, sometimes, European or Commonwealth (Australia/New Zealand) experts that we need to broaden our perspectives and now I can add: or at least acknowledge (e.g. transatlantic) that the perspectives taken are reflective of a rather narrow range of countries.

Now getting to the report, here’s more from a November 21, 2017 University of Cambridge press release,

Human genome editing, 3D-printed replacement organs and artificial photosynthesis – the field of bioengineering offers great promise for tackling the major challenges that face our society. But as a new article out today highlights, these developments provide both opportunities and risks in the short and long term.

Rapid developments in the field of synthetic biology and its associated tools and methods, including more widely available gene editing techniques, have substantially increased our capabilities for bioengineering – the application of principles and techniques from engineering to biological systems, often with the goal of addressing ‘real-world’ problems.

In a feature article published in the open access journal eLife, an international team of experts led by Dr Bonnie Wintle and Dr Christian R. Boehm from the Centre for the Study of Existential Risk at the University of Cambridge, capture perspectives of industry, innovators, scholars, and the security community in the UK and US on what they view as the major emerging issues in the field.

Dr Wintle says: “The growth of the bio-based economy offers the promise of addressing global environmental and societal challenges, but as our paper shows, it can also present new kinds of challenges and risks. The sector needs to proceed with caution to ensure we can reap the benefits safely and securely.”

The report is intended as a summary and launching point for policy makers across a range of sectors to further explore those issues that may be relevant to them.

Among the issues highlighted by the report as being most relevant over the next five years are:

Artificial photosynthesis and carbon capture for producing biofuels

If technical hurdles can be overcome, such developments might contribute to the future adoption of carbon capture systems, and provide sustainable sources of commodity chemicals and fuel.

Enhanced photosynthesis for agricultural productivity

Synthetic biology may hold the key to increasing yields on currently farmed land – and hence helping address food security – by enhancing photosynthesis and reducing pre-harvest losses, as well as reducing post-harvest and post-consumer waste.

Synthetic gene drives

Gene drives promote the inheritance of preferred genetic traits throughout a species, for example to prevent malaria-transmitting mosquitoes from breeding. However, this technology raises questions about whether it may alter ecosystems [emphasis mine], potentially even creating niches where a new disease-carrying species or new disease organism may take hold.

Human genome editing

Genome engineering technologies such as CRISPR/Cas9 offer the possibility to improve human lifespans and health. However, their implementation poses major ethical dilemmas. It is feasible that individuals or states with the financial and technological means may elect to provide strategic advantages to future generations.

Defence agency research in biological engineering

The areas of synthetic biology in which some defence agencies invest raise the risk of ‘dual-use’. For example, one programme intends to use insects to disseminate engineered plant viruses that confer traits to the target plants they feed on, with the aim of protecting crops from potential plant pathogens – but such technologies could plausibly also be used by others to harm targets.

In the next five to ten years, the authors identified areas of interest including:

Regenerative medicine: 3D printing body parts and tissue engineering

While this technology will undoubtedly ease suffering caused by traumatic injuries and a myriad of illnesses, reversing the decay associated with age is still fraught with ethical, social and economic concerns. Healthcare systems would rapidly become overburdened by the cost of replenishing body parts of citizens as they age and could lead new socioeconomic classes, as only those who can pay for such care themselves can extend their healthy years.

Microbiome-based therapies

The human microbiome is implicated in a large number of human disorders, from Parkinson’s to colon cancer, as well as metabolic conditions such as obesity and type 2 diabetes. Synthetic biology approaches could greatly accelerate the development of more effective microbiota-based therapeutics. However, there is a risk that DNA from genetically engineered microbes may spread to other microbiota in the human microbiome or into the wider environment.

Intersection of information security and bio-automation

Advancements in automation technology combined with faster and more reliable engineering techniques have resulted in the emergence of robotic ‘cloud labs’ where digital information is transformed into DNA then expressed in some target organisms. This opens the possibility of new kinds of information security threats, which could include tampering with digital DNA sequences leading to the production of harmful organisms, and sabotaging vaccine and drug production through attacks on critical DNA sequence databases or equipment.

Over the longer term, issues identified include:

New makers disrupt pharmaceutical markets

Community bio-labs and entrepreneurial startups are customizing and sharing methods and tools for biological experiments and engineering. Combined with open business models and open source technologies, this could herald opportunities for manufacturing therapies tailored to regional diseases that multinational pharmaceutical companies might not find profitable. But this raises concerns around the potential disruption of existing manufacturing markets and raw material supply chains as well as fears about inadequate regulation, less rigorous product quality control and misuse.

Platform technologies to address emerging disease pandemics

Emerging infectious diseases—such as recent Ebola and Zika virus disease outbreaks—and potential biological weapons attacks require scalable, flexible diagnosis and treatment. New technologies could enable the rapid identification and development of vaccine candidates, and plant-based antibody production systems.

Shifting ownership models in biotechnology

The rise of off-patent, generic tools and the lowering of technical barriers for engineering biology has the potential to help those in low-resource settings, benefit from developing a sustainable bioeconomy based on local needs and priorities, particularly where new advances are made open for others to build on.

Dr Jenny Molloy comments: “One theme that emerged repeatedly was that of inequality of access to the technology and its benefits. The rise of open source, off-patent tools could enable widespread sharing of knowledge within the biological engineering field and increase access to benefits for those in developing countries.”

Professor Johnathan Napier from Rothamsted Research adds: “The challenges embodied in the Sustainable Development Goals will require all manner of ideas and innovations to deliver significant outcomes. In agriculture, we are on the cusp of new paradigms for how and what we grow, and where. Demonstrating the fairness and usefulness of such approaches is crucial to ensure public acceptance and also to delivering impact in a meaningful way.”

Dr Christian R. Boehm concludes: “As these technologies emerge and develop, we must ensure public trust and acceptance. People may be willing to accept some of the benefits, such as the shift in ownership away from big business and towards more open science, and the ability to address problems that disproportionately affect the developing world, such as food security and disease. But proceeding without the appropriate safety precautions and societal consensus—whatever the public health benefits—could damage the field for many years to come.”

The research was made possible by the Centre for the Study of Existential Risk, the Synthetic Biology Strategic Research Initiative (both at the University of Cambridge), and the Future of Humanity Institute (University of Oxford). It was based on a workshop co-funded by the Templeton World Charity Foundation and the European Research Council under the European Union’s Horizon 2020 research and innovation programme.

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

A transatlantic perspective on 20 emerging issues in biological engineering by Bonnie C Wintle, Christian R Boehm, Catherine Rhodes, Jennifer C Molloy, Piers Millett, Laura Adam, Rainer Breitling, Rob Carlson, Rocco Casagrande, Malcolm Dando, Robert Doubleday, Eric Drexler, Brett Edwards, Tom Ellis, Nicholas G Evans, Richard Hammond, Jim Haseloff, Linda Kahl, Todd Kuiken, Benjamin R Lichman, Colette A Matthewman, Johnathan A Napier, Seán S ÓhÉigeartaigh, Nicola J Patron, Edward Perello, Philip Shapira, Joyce Tait, Eriko Takano, William J Sutherland. eLife; 14 Nov 2017; DOI: 10.7554/eLife.30247

This paper is open access and the editors have included their notes to the authors and the authors’ response.

You may have noticed that I highlighted a portion of the text concerning synthetic gene drives. Coincidentally I ran across a November 16, 2017 article by Ed Yong for The Atlantic where the topic is discussed within the context of a project in New Zealand, ‘Predator Free 2050’ (Note: A link has been removed),

Until the 13th century, the only land mammals in New Zealand were bats. In this furless world, local birds evolved a docile temperament. Many of them, like the iconic kiwi and the giant kakapo parrot, lost their powers of flight. Gentle and grounded, they were easy prey for the rats, dogs, cats, stoats, weasels, and possums that were later introduced by humans. Between them, these predators devour more than 26 million chicks and eggs every year. They have already driven a quarter of the nation’s unique birds to extinction.

Many species now persist only in offshore islands where rats and their ilk have been successfully eradicated, or in small mainland sites like Zealandia where they are encircled by predator-proof fences. The songs in those sanctuaries are echoes of the New Zealand that was.

But perhaps, they also represent the New Zealand that could be.

In recent years, many of the country’s conservationists and residents have rallied behind Predator-Free 2050, an extraordinarily ambitious plan to save the country’s birds by eradicating its invasive predators. Native birds of prey will be unharmed, but Predator-Free 2050’s research strategy, which is released today, spells doom for rats, possums, and stoats (a large weasel). They are to die, every last one of them. No country, anywhere in the world, has managed such a task in an area that big. The largest island ever cleared of rats, Australia’s Macquarie Island, is just 50 square miles in size. New Zealand is 2,000 times bigger. But, the country has committed to fulfilling its ecological moonshot within three decades.

In 2014, Kevin Esvelt, a biologist at MIT, drew a Venn diagram that troubles him to this day. In it, he and his colleagues laid out several possible uses for gene drives—a nascent technology for spreading designer genes through groups of wild animals. Typically, a given gene has a 50-50 chance of being passed to the next generation. But gene drives turn that coin toss into a guarantee, allowing traits to zoom through populations in just a few generations. There are a few natural examples, but with CRISPR, scientists can deliberately engineer such drives.

Suppose you have a population of rats, roughly half of which are brown, and the other half white. Now, imagine there is a gene that affects each rat’s color. It comes in two forms, one leading to brown fur, and the other leading to white fur. A male with two brown copies mates with a female with two white copies, and all their offspring inherit one of each. Those offspring breed themselves, and the brown and white genes continue cascading through the generations in a 50-50 split. This is the usual story of inheritance. But you can subvert it with CRISPR, by programming the brown gene to cut its counterpart and replace it with another copy of itself. Now, the rats’ children are all brown-furred, as are their grandchildren, and soon the whole population is brown.

Forget fur. The same technique could spread an antimalarial gene through a mosquito population, or drought-resistance through crop plants. The applications are vast, but so are the risks. In theory, gene drives spread so quickly and relentlessly that they could rewrite an entire wild population, and once released, they would be hard to contain. If the concept of modifying the genes of organisms is already distasteful to some, gene drives magnify that distaste across national, continental, and perhaps even global scales.

These excerpts don’t do justice to this thought-provoking article. If you have time, I recommend reading it in its entirety  as it provides some insight into gene drives and, with some imagination on the reader’s part, the potential for the other technologies discussed in the report.

One last comment, I notice that Eric Drexler is cited as on the report’s authors. He’s familiar to me as K. Eric Drexler, the author of the book that popularized nanotechnology in the US and other countries, Engines of Creation (1986) .

Café Scientifique Vancouver talk on January 30, 2018 and a couple of February 2018 art/sci events in Toronto

Vancouver

This could be a first for Café Scientifique Vancouver. From a January 28, 2018 Café Scientifique Vancouver announcement (received via email)

This is a reminder that our next café with biotech entrepreneur Dr.Andrew Tait (TUESDAY, JANUARY 30TH [2018] at 7:30PM) in the back room of YAGGER'S DOWNTOWN (433 W Pender).

COMBINING TRADITIONAL NATURAL MEDICINES WITH SCIENTIFIC RESEARCH: UNVEILING THE POTENTIAL OF THE MANDARIN ORANGE PEEL

The orange peel is something most of us may think of as a throw-away compost item, but it is so much more. Travel back in time 9,000 years to China, where orange peel was found in the first fermented alcoholic beverage, and return to today, where mandarin orange peel remains one of China’s top selling herbs that promotes digestion. Now meet Tait Laboratories Inc., a company that was founded based on one chemistry Ph.D. student’s idea, that mandarin orange peel has the potential to reverse incurable neurodegenerative diseases like multiple sclerosis. You will learn about the company’s journey through a scientific lens, from its early days to the present, having developed a mandarin orange peel product sold across Canada in over 1,000 stores including 400 Rexall pharmacies. You will leave with a basic understanding of how herbal products like the company’s mandarin orange peel-based product are developed and brought to market in Canada, and about the science that is required to substantiate health claims on this and other exciting new botanical products.

Bio:

Dr. Andrew Tait is the founder of Tait Laboratories Inc., a company devoted to developing natural medicines from agricultural bi-products. After a B.Sc. in Biochemistry and M.Sc. in Chemistry from Concordia University (Montreal), he completed a Ph.D. in Chemistry at the
University of British Columbia [UBC].

Inspired by his thesis work on multiple sclerosis, he subsequently identified Traditional Chinese Medicines as having potential to treat a wide range of chronic diseases; he founded the company while finishing his graduate studies.

In 2012, he was invited to Ottawa to be awarded the NSERC [{Canada} Natural Sciences and Engineering Research Council] Innovation Challenge Award, for successfully translating his Ph.D. research to an entrepreneurial venture. In 2014, he was awarded the BC Food Processors Association “Rising Star” award.

Dr. Tait is a regularly invited speaker on the topics of entrepreneurship and the science supporting natural health products; he was keynote speaker in 2012 at the Annual Symposium of the Boucher Institute of Naturopathic Medicine (Vancouver) and in 2016 at the
Functional Foods and Natural Health Products Graduate Research Symposium (Winnipeg).

Supported by the Futurpreneur Canada, the Bank of Development of Canada, the UBC’s Entrepreneurship@UBC program, and the NSERC  and NRC  [{Canada} National Research Council] Industry Research Assistance Program (IRAP), he works with industrial and academic researchers developing safe, affordable, and clinically proven medicines. He successfully launched MS+ Mandarin Skin PlusÒ, a patent-pending digestive product now on shelf in over 1000 pharmacies and health food stores across Canada, including 400 Rexall pharmacies.

Dr. Tait mentors young companies as an Entrepreneur in Residence at both SFU [Simon Fraser University] Coast Capital Savings Venture Connection and also the Health Tech Innovation Hub and he also volunteers his time to mentor students of the Student Biotechnology Network.

Lest it be forgotten, many drugs and therapeutic agents are based on natural remedies; a fact often ignored in the discussion about drugs and natural remedies. In any event, I am surprised this talk is being hosted by Café Scientifique Vancouver which has tended to more ‘traditional’ (i.e., university academic) presentations without any hint of ‘alternative’ or ‘entrepreneurial’ aspects. I wonder if this is the harbinger of new things to come from the Café Scientifique Vancouver community.

Meanwhile, interested parties can find out more about Tait Laboratories on their company website. They are selling one product at this time (from the MS+ [Mandarin Skin Plus] product webpage,

MS+™ (Mandarin Skin Plus) is a revolutionary natural health product that aids with digestion and promotes gastrointestinal health. It is a patent-pending proprietary extract based on dry-aged mandarin orange peel, an ancient Traditional Chinese Medicine. This remedy has been safely used for centuries to relieve bloating, indigestion, diarrhea, nausea, upset stomach, cough with phlegm. Experience ULTIMATE DIGESTIVE RELIEF and top gastrointestinal health for only about a dollar a day!

Directions: take one capsule twice a day, up to six capsules per day. Swallow capsule directly OR dissolve powder in water.
60 vegan capsules for ~ 1 month supply

I would have liked to have seen a list of research papers and discussion of human clinical trials regarding their ‘digestive’ product. Will Tait be discussing his research and results into what seems to be a new direction (i.e., the use of mandarin skin peel-derived therapeutics for neurodegenerative diseases)?

I don’t think I’m going to make it to the talk but should anyone who attends care to answer the question, please feel free to add a comment.

ArtSci Salon in Toronto

2018 is proving to be an active year for the ArtSci Salon folks in Toronto. They’ve just finished hosting a January 24-25, 2018 workshop and January 26, 2018 panel discussion on the gene-editing tool CRISPR/CAS9 (see my January 10, 2018 posting for a description).

Now they’ve announced another workshop and panel discussion on successive nights in February, the topic being: cells. From a January 29, 2018 ArtSci Salon announcement (received via email), Note: The panel discussion is listed first, then the workshop, then the artists’ biographies,

FROM CELL TO CANVAS: CREATIVE EXPLORATIONS OF THE MICROSCOPIC [panel discussion]

From the complex forms of the cell to the colonies created by the microbiota; from the undetectable chemical reactions activated by enzymes and natural processes to the environmental information captured through data visualization, the five local and international artists presenting tonight have developed a range of very diverse practices all inspired by the invisible, the undetectable and the microscopic.

We invite you to an evening of artist talks and discussion on the creative process of exploring the microscopic and using living organisms in art, on its potentials and implication for science and its popular dissemination, as well as on its ethics.

WITH:
Robyn Crouch
Mellissa Fisher
JULIA KROLIK
SHAVON MADDEN
TOSCA TERAN

FRIDAY, FEB 9, 2018
6:00-8:00 PM
THE FIELDS INSTITUTE
222 COLLEGE STREET,
RM 230

[Go to this page for access to registration]

FROM CELL TO CANVAS: CREATIVE EXPLORATIONS OF THE MICROSCOPIC [workshop]

THE EVENT WILL BE FOLLOWED BY A WORKSHOP BY: MELLISSA FISHER, SHAVON MADDEN AND JULIA KROLIK
FEB. 10, 2018
11:00AM-5:00PM
AT HACKLAB,
1266 Queen St West

[Go to this page for access to registration]

Workshop:

Design My Microbiome

Artist Mellissa Fisher invites participants to mould parts of her body in agar to create their own microbial version of her, alongside producing their own microbial portrait with painting techniques.

Cooking with the Invasive

Artist Shavon Madden invites participants to discuss invasive species like garlic mustard and cook invasive species whilst exploring, do species which we define and brand as invasive simply have no benefits?

Intoduction to Biological Staining

Artist & Scientist Julia Krolik invites participants to learn about 3 different types of biological staining and have a chance to try staining procedures.

BIOS:

ROBYN CROUCH
The symbolic imagery that comes through Robyn’s work invites one’s gaze inward to the cellular realms. There, one discovers playful depictions of chemical processes; the unseen lattice upon which our macro­cosmic world is constructed. Technological advancements create windows into this molecular realm, and human consciousness acts as the interface between the seen and the unseen worlds. In her functional ceramic work, the influence of Chinese and Japanese tea ceremony encourages contem­plation and appreciation of a quiet
moment. The viewer-participant can lose their train of thought while meandering through geometry and biota, con­nected by strands of double-helical DNA. A flash of recognition, a momentary mirror.

MELLISSA FISHER
Mellissa Fisher is a British Bio Artist based in Kent. Her practice explores the invisible world on our skin by using living organisms and by creating sculptures made with agar to show the public what the surface of our skin really looks like. She is best known for her work with bacteria and works extensively with collaborators in microbiology and immunology. She has exhibited an installation _ “Microbial Me”_with Professor Mark Clements and Dr Richard Harvey at The Eden Project for their permanent exhibition _“The Invisible You: The Human
Microbiome”._The installation included a living portrait in bacteria of the artists face as well as a time-lapse film of the sculpture growing.

JULIA KROLIK
Julia Krolik is a creative director, entrepreneur, scientist and award-winning artist. Her diverse background enables a rare cross-disciplinary empathy, and she continuously advocates for both art and science through several initiatives. Julia is the founder of Art the Science, a non-profit organization dedicated to facilitating artist residencies in scientific research laboratories to foster Canadian science-art culture and expand scientific knowledge communication to benefit the public. Through her consulting agency Pixels and Plans, Julia works with private and public organizations, helping them with strategy, data visualization and knowledge mobilization, often utilizing creative technology and skills-transfer workshops.

SHAVON MADDEN
Shavon Madden is a Brampton based artist, specializing in sculptural, performance and instillation based work exploring the social injustices inflicted on the environment and its creatures. Her work focuses on challenging social-environmental and political ethics, through the embodied experience and feelings of self. She graduated from the University of Toronto Specializing in Art and Art History, along with studies in Environmental Science and will be on her way to Edinburgh for her MFA. Shavon has had works shown at Shelly Peterson, the Burlington Art Gallery and the Art Gallery of Mississauga, among many others. Website: www.greenheartartistry.com [4]

TOSCA TERAN
Working with metal for over 30+ years, Tosca was introduced to glass as an artistic medium in 2004. Through developing bodies of work incorporating metal + glass Tosca has been awarded scholarships at The Corning Museum of Glass, Pilchuck Glass School and The Penland school of Crafts. Her work has been featured at SOFA New York, Culture Canada,
Metalsmith Magazine, The Toronto Design Exchange, and the Memphis Metal Museum. She has been awarded residencies at Gullkistan, Nes, and the Ayatana Research Program. A long-term guest artist instructor at the Ontario Science Centre, Tosca continues to explore materials, code, BioArt, SciArt and teach Metal + Glass courses out of her studio in Toronto.

It seems that these February events and the two events with Marta de Menezes are part of the FACTT (transdisciplinary and transnational festival of art and science) Toronto, from the FACTT Toronto webpage,

FACTT Toronto – Festival of Art & Science posted in: blog, events

The Arte Institute, in partnership with Cultivamos Cultura and ArtSi Salon, has the pleasure to announce FACTT – Festival of Art & Science in Toronto.

The Festival took place in Lisbon, New York, Mexico, Berlin and will continue in Toronto.
Exhibition: The Cabinet Project/ Art Sci Salon / FACTT

Artists:

Andrew Carnie
Elaine Whittaker
Erich Berger
Joana Ricou
Ken Rinaldo
Laura Beloff and Maria Antonia Gonzalez Valerio
Marta de Menezes and Luís Graça
Pedro Cruz

Dates: Jan 26- feb 15 [2018 {sic}]

Where: Meet us on Jan 26 [2018] in the Lobby of the Physics Department, 255 Huron Street
University of Toronto
When: 4:45 PM

You may want to keep an eye on the ArtSci Salon website although I find their posting schedule a bit erratic. Sometimes, I get email notices for events that aren’t yet listed on their website.

CRISPR/Cas9 as a tool for artists (Art/sci Salon January 2018 events in Toronto, Canada) and an event in Winnipeg, Canada

The Art/Sci Salon in Toronto, Canada is offering a workshop and a panel discussion (I think) on the topic of CRISPR( (clustered regularly interspaced short palindromic repeats)/Cas9.

CRISPR Cas9 Workshop with Marta De Menezes

From its Art/Sci Salon event page (on Eventbrite),

This is a two day intensive workshop on

Jan. 24 5:00-9:00 pm
and
Jan. 25 5:00-9:00 pm

This workshop will address issues pertaining to the uses, ethics, and representations of CRISPR-cas9 genome editing system; and the evolution of bioart as a cultural phenomenon . The workshop will focus on:

1. Scientific strategies and ethical issues related to the modification of organisms through the most advanced technology;

2. Techniques and biological materials to develop and express complex concepts into art objects.

This workshop will introduce knowledge, methods and living material from the life sciences to the participants. The class will apply that novel information to the creation of art. Finally, the key concepts, processes and knowledge from the arts will be discussed and related to scientific research. The studio-­‐lab portion of the course will focus on the mastering and understanding of the CRISPR – Cas9 technology and its revolutionary applications. The unparalleled potential of CRISPR ‐ Cas9 for genome editing will be directly assessed as the participants will use the method to make artworks and generate meaning through such a technique. The participants will be expected to complete one small project by the end of the course. In developing and completing these projects, participants will be asked to present their ideas/work to the instructors and fellow participants. As part of the course, participants are expected to document their work/methodology/process by keeping a record of processes, outcomes, and explorations.

This is a free event. Go here to register.

Do CRISPR monsters dream of synthetic futures?

This second event in Toronto seems to be a panel discussion; here’s more from its Art/Sci Salon event page (on Eventbrite),

The term CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) refers to a range of novel gene editing systems which can be programmed to edit DNA at precise locations. It allows the permanent modification of the genes in cells of living organisms. CRISPR enables novel basic research and promises a wide range of possible applications from biomedicine and agriculture to environmental challenges.

The surprising simplicity of CRISPR and its potentials have led to a wide range of reactions. While some welcome it as a gene editing revolution able to cure diseases that are currently fatal, others urge for a worldwide moratorium, especially when it comes to human germline modifications. The possibility that CRISPR may allow us to intervene in the evolution of organisms has generated particularly divisive thoughts: is gene editing going to cure us all? Or is it opening up a new era of designer babies and new types of privileges measured at the level of genes? Could the relative easiness of the technique allow individuals to modify bodies, identities, sexuality, to create new species and races? will it create new monsters? [emphasis mine] These are all topics that need to be discussed. With this panel/discussion, we wish to address technical, ethical, and creative issues arising from the futuristic scenarios promised by CRISPR.

Our Guests:

Marta De Menezes, Director, Cultivamos Cultura

Dalila Honorato, Assistant Professor, Ionian University

Mark Lipton, Professor, University of Guelph

Date: January 26, 2018

Time: 6:00-8:00 pm

Location: The Fields Institute for Research in Mathematical Sciences
222 College Street, Toronto, ON

Events Facilitators: Roberta Buiani and Stephen Morris (ArtSci Salon) and Nina Czegledy (Leonardo Network)

Bios:

Marta de Menezes is a Portuguese artist (b. Lisbon, 1975) with a degree in Fine Arts by the University in Lisbon, a MSt in History of Art and Visual Culture by the University of Oxford, and a PhD candidate at the University of Leiden. She has been exploring the intersection between Art and Biology, working in research laboratories demonstrating that new biological technologies can be used as new art medium. Her work has been presented internationally in exhibitions, articles and lectures. She is currently the artistic director of Ectopia, an experimental art laboratory in Lisbon, and Director of Cultivamos Cultura in the South of Portugal. http://martademenezes.com

Dalila Honorato, Ph.D., is currently Assistant Professor in Media Aesthetics and Semiotics at the Ionian University in Greece where she is one of the founding members of the Interactive Arts Lab. She is the head of the organizing committee of the conference “Taboo-Transgression-Transcendence in Art & Science” and developer of the studies program concept of the Summer School in Hybrid Arts. She is a guest faculty at the PhD studies program of the Institutum Studiorum Humanitatis in Alma Mater Europaea, Slovenia, and a guest member of the Science Art Philosophy Lab integrated in the Center of Philosophy of Sciences of the University of Lisbon, Portugal. Her research focus is on embodiment in the intersection of performing arts and new media.

Mark Lipton works in the College of Arts; in the School of English and Theatre Studies, and Guelph’s Program in Media Studies. Currently, his work focuses on queering media ecological perspectives of technology’s role in education, with emerging questions about haptics and the body in performance contexts, and political outcomes of neo-liberal economics within Higher Education.

ArtSci Salon thanks the Fields Institute and the Bonham Center for Sexual Diversity Studies (U of T), and the McLuhan Centre for Culture and Technology for their support. We are grateful to the members of DIYBio Toronto and Hacklab for hosting Marta’s workshop.

This series of event is promoted and facilitated as part of FACTT Toronto

LASER – Leonardo Art Science Evening Rendezvous is a project of Leonardo® /ISAST (International Society for the Arts Sciences and Technology)

Go here to click on the Register button.

For anyone who didn’t recognize (or, like me, barely remembers what it means) the title’s reference is to a famous science fiction story by Philip K. Dick. Here’s more from the Do Androids Dream of Electric Sheep? Wikipedia entry (Note: Links have been removed),

Do Androids Dream of Electric Sheep? (retitled Blade Runner: Do Androids Dream of Electric Sheep? in some later printings) is a science fiction novel by American writer Philip K. Dick, first published in 1968. The novel is set in a post-apocalyptic San Francisco, where Earth’s life has been greatly damaged by nuclear global war. Most animal species are endangered or extinct from extreme radiation poisoning, so that owning an animal is now a sign of status and empathy, an attitude encouraged towards animals. The book served as the primary basis for the 1982 film Blade Runner, and many elements and themes from it were used in its 2017 sequel Blade Runner 2049.

The main plot follows Rick Deckard, a bounty hunter who is tasked with “retiring” (i.e. killing) six escaped Nexus-6 model androids, while a secondary plot follows John Isidore, a man of sub-par IQ who aids the fugitive androids. In connection with Deckard’s mission, the novel explores the issue of what it is to be human. Unlike humans, the androids are said to possess no sense of empathy.

I wonder why they didn’t try to reference Orphan Black (its Wikipedia entry)? That television series was all about biotechnology. If not Orphan Black, what about a Frankenstein reference? It’s the 200th anniversary this year (2018) of the publication of the book which is the forerunner to all the cautionary tales that have come after.

Could CRISPR (clustered regularly interspaced short palindromic repeats) be weaponized?

On the occasion of an American team’s recent publication of research where they edited the germline (embryos), I produced a three-part series about CRISPR (clustered regularly interspaced short palindromic repeats), sometimes referred to as CRISPR/Cas9, (links offered at end of this post).

Somewhere in my series, there’s a quote about how CRISPR could be used as a ‘weapon of mass destruction’ and it seems this has been a hot topic for the last year or so as James Revill, research fellow at the University of Sussex, references in his August 31, 2017 essay on theconversation.com (h/t phys.org August 31, 2017 news item), Note: Links have been removed,

The gene editing technique CRISPR has been in the limelight after scientists reported they had used it to safely remove disease in human embryos for the first time. This follows a “CRISPR craze” over the last couple of years, with the number of academic publications on the topic growing steadily.

There are good reasons for the widespread attention to CRISPR. The technique allows scientists to “cut and paste” DNA more easily than in the past. It is being applied to a number of different peaceful areas, ranging from cancer therapies to the control of disease carrying insects.

Some of these applications – such as the engineering of mosquitoes to resist the parasite that causes malaria – effectively involve tinkering with ecosystems. CRISPR has therefore generated a number of ethical and safety concerns. Some also worry that applications being explored by defence organisations that involve “responsible innovation in gene editing” may send worrying signals to other states.

Concerns are also mounting that gene editing could be used in the development of biological weapons. In 2016, Bill Gates remarked that “the next epidemic could originate on the computer screen of a terrorist intent on using genetic engineering to create a synthetic version of the smallpox virus”. More recently, in July 2017, John Sotos, of Intel Health & Life Sciences, stated that gene editing research could “open up the potential for bioweapons of unimaginable destructive potential”.

An annual worldwide threat assessment report of the US intelligence community in February 2016 argued that the broad availability and low cost of the basic ingredients of technologies like CRISPR makes it particularly concerning.

A Feb. 11, 2016 news item on sciencemagazine.org offers a précis of some of the reactions while a February 9, 2016 article by Antonio Regalado for the Massachusetts Institute of Technology’s MIT Technology Review delves into the matter more deeply,

Genome editing is a weapon of mass destruction.

That’s according to James Clapper, [former] U.S. director of national intelligence, who on Tuesday, in the annual worldwide threat assessment report of the U.S. intelligence community, added gene editing to a list of threats posed by “weapons of mass destruction and proliferation.”

Gene editing refers to several novel ways to alter the DNA inside living cells. The most popular method, CRISPR, has been revolutionizing scientific research, leading to novel animals and crops, and is likely to power a new generation of gene treatments for serious diseases (see “Everything You Need to Know About CRISPR’s Monster Year”).

It is gene editing’s relative ease of use that worries the U.S. intelligence community, according to the assessment. “Given the broad distribution, low cost, and accelerated pace of development of this dual-use technology, its deliberate or unintentional misuse might lead to far-reaching economic and national security implications,” the report said.

The choice by the U.S. spy chief to call out gene editing as a potential weapon of mass destruction, or WMD, surprised some experts. It was the only biotechnology appearing in a tally of six more conventional threats, like North Korea’s suspected nuclear detonation on January 6 [2016], Syria’s undeclared chemical weapons, and new Russian cruise missiles that might violate an international treaty.

The report is an unclassified version of the “collective insights” of the Central Intelligence Agency, the National Security Agency, and half a dozen other U.S. spy and fact-gathering operations.

Although the report doesn’t mention CRISPR by name, Clapper clearly had the newest and the most versatile of the gene-editing systems in mind. The CRISPR technique’s low cost and relative ease of use—the basic ingredients can be bought online for $60—seems to have spooked intelligence agencies.

….

However, one has to be careful with the hype surrounding new technologies and, at present, the security implications of CRISPR are probably modest. There are easier, cruder methods of creating terror. CRISPR would only get aspiring biological terrorists so far. Other steps, such as growing and disseminating biological weapons agents, would typically be required for it to become an effective weapon. This would require additional skills and places CRISPR-based biological weapons beyond the reach of most terrorist groups. At least for the time being.

A July 5, 2016 opinion piece by Malcolm Dando for Nature argues for greater safeguards,

In Geneva next month [August 2016], officials will discuss updates to the global treaty that outlaws the use of biological weapons. The 1972 Biological Weapons Convention (BWC) was the first agreement to ban an entire class of weapons, and it remains a crucial instrument to stop scientific research on viruses, bacteria and toxins from being diverted into military programmes.

The BWC is the best route to ensure that nations take the biological-weapons threat seriously. Most countries have struggled to develop and introduce strong and effective national programmes — witness the difficulty the United States had in agreeing what oversight system should be applied to gain-of-function experiments that created more- dangerous lab-grown versions of common pathogens.

As scientific work advances — the CRISPR gene-editing system has been flagged as the latest example of possible dual-use technology — this treaty needs to be regularly updated. This is especially important because it has no formal verification system. Proposals for declarations, monitoring visits and inspections were vetoed by the United States in 2001, on the grounds that such verification threatened national security and confidential business information.

Even so, issues such as the possible dual-use threat from gene-editing systems will not be easily resolved. But we have to try. Without the involvement of the BWC, codes of conduct and oversight systems set up at national level are unlikely to be effective. The stakes are high, and after years of fumbling, we need strong international action to monitor and assess the threats from the new age of biological techniques.

Revill notes the latest BWC agreement and suggests future directions,

This convention is imperfect and lacks a way to ensure that states are compliant. Moreover, it has not been adequately “tended to” by its member states recently, with the last major meeting unable to agree a further programme of work. Yet it remains the cornerstone of an international regime against the hostile use of biology. All 178 state parties declared in December of 2016 their continued determination “to exclude completely the possibility of the use of (biological) weapons, and their conviction that such use would be repugnant to the conscience of humankind”.

These states therefore need to address the hostile potential of CRISPR. Moreover, they need to do so collectively. Unilateral national measures, such as reasonable biological security procedures, are important. However, preventing the hostile exploitation of CRISPR is not something that can be achieved by any single state acting alone.

As such, when states party to the convention meet later this year, it will be important to agree to a more systematic and regular review of science and technology. Such reviews can help with identifying and managing the security risks of technologies such as CRISPR, as well as allowing an international exchange of information on some of the potential benefits of such technologies.

Most states supported the principle of enhanced reviews of science and technology under the convention at the last major meeting. But they now need to seize the opportunity and agree on the practicalities of such reviews in order to prevent the convention being left behind by developments in science and technology.

Experts (military, intelligence, medical, etc.) are not the only ones concerned about CRISPR according to a February 11, 2016 article by Sharon Begley for statnews.com (Note: A link has been removed),

Most Americans oppose using powerful new technology to alter the genes of unborn babies, according to a new poll — even to prevent serious inherited diseases.

They expressed the strongest disapproval for editing genes to create “designer babies” with enhanced intelligence or looks.

But the poll, conducted by STAT and Harvard T.H. Chan School of Public Health, found that people have mixed, and apparently not firm, views on emerging genetic techniques. US adults are almost evenly split on whether the federal government should fund research on editing genes before birth to keep children from developing diseases such as cystic fibrosis or Huntington’s disease.

“They’re not against scientists trying to improve [genome-editing] technologies,” said Robert Blendon, professor of health policy and political analysis at Harvard’s Chan School, perhaps because they recognize that one day there might be a compelling reason to use such technologies. An unexpected event, such as scientists “eliminating a terrible disease” that a child would have otherwise inherited, “could change people’s views in the years ahead,” Blendon said.

But for now, he added, “people are concerned about editing the genes of those who are yet unborn.”

A majority, however, wants government regulators to approve gene therapy to treat diseases in children and adults.

The STAT-Harvard poll comes as scientists and policy makers confront the ethical, social, and legal implications of these revolutionary tools for changing DNA. Thanks to a technique called CRISPR-Cas9, scientists can easily, and with increasing precision, modify genes through the genetic analog of a computer’s “find and replace” function.

I find it surprising that there’s resistance to removing diseases found in the germline (embryos). When they were doing public consultations on nanotechnology, the one area where people tended to be quite open to research was health and medicine. Where food was concerned however, people had far more concerns.

If you’re interested in the STAT-Harvard poll, you can find it here. As for James Revill, he has written a more substantive version of this essay as a paper, which is available here.

On a semi-related note, I found STAT (statnews.com) to be a quite interesting and accessibly written online health science journal. Here’s more from the About Us page (Note: A link has been removed),

What’s STAT all about?
STAT is a national publication focused on finding and telling compelling stories about health, medicine, and scientific discovery. We produce daily news, investigative articles, and narrative projects in addition to multimedia features. We tell our stories from the places that matter to our readers — research labs, hospitals, executive suites, and political campaigns.

Why did you call it STAT?
In medical parlance, “stat” means important and urgent, and that’s what we’re all about — quickly and smartly delivering good stories. Read more about the origins of our name here.

Who’s behind the new publication?
STAT is produced by Boston Globe Media. Our headquarters is located in Boston but we have bureaus in Washington, New York, Cleveland, Atlanta, San Francisco, and Los Angeles. It was started by John Henry, the owner of Boston Globe Media and the principal owner of the Boston Red Sox. Rick Berke is executive editor.

So is STAT part of The Boston Globe?
They’re distinct properties but the two share content and complement one another.

Is it free?
Much of STAT is free. We also offer STAT Plus, a premium subscription plan that includes exclusive reporting about the pharmaceutical and biotech industries as well as other benefits. Learn more about it here.

Who’s working for STAT?
Some of the best-sourced science, health, and biotech journalists in the country, as well as motion graphics artists and data visualization specialists. Our team includes talented writers, editors, and producers capable of the kind of explanatory journalism that complicated science issues sometimes demand.

Who’s your audience?
You. Even if you don’t work in science, have never stepped foot in a hospital, or hated high school biology, we’ve got something for you. And for the lab scientists, health professionals, business leaders, and policy makers, we think you’ll find coverage here that interests you, too. The world of health, science, and medicine is booming and yielding fascinating stories. We explore how they affect us all.

….

As promised, here are the links to my three-part series on CRISPR,

Part 1 opens the series with a basic description of CRISPR and the germline research that occasioned the series along with some of the other (non-weapon) ethical issues and patent disputes that are arising from this new technology. CRISPR and editing the germline in the US (part 1 of 3): In the beginning

Part 2 covers three critical responses to the reporting and between them describe the technology in more detail and the possibility of ‘designer babies’.  CRISPR and editing the germline in the US (part 2 of 3): ‘designer babies’?

Part 3 is all about public discussion or, rather, the lack of and need for according to a couple of social scientists. Informally, there is some discussion via pop culture and Joelle Renstrom notes although she is focused on the larger issues touched on by the television series, Orphan Black and as I touch on in my final comments. CRISPR and editing the germline in the US (part 3 of 3): public discussions and pop culture

Finally, I hope to stumble across studies from other countries about how they are responding to the possibilities presented by CRISPR/Cas9 so that I can offer a more global perspective than this largely US perspective. At the very least, it would be interesting to find it if there differences.

CRISPR corn to come to market in 2020

It seems most of the recent excitement around CRISPR/CAS9 (clustered regularly interspaced short palindromic repeats) has focused on germline editing, specifically human embryos. Most people don’t realize that the first ‘CRISPR’ product is slated to enter the US market in 2020. A June 14, 2017 American Chemical Society news release (also on EurekAlert) provides a preview,

The gene-editing technique known as CRISPR/Cas9 made a huge splash in the news when it was initially announced. But the first commercial product, expected around 2020, could make it to the market without much fanfare: It’s a waxy corn destined to contribute to paper glue and food thickeners. The cover story of Chemical & Engineering News (C&EN), the weekly newsmagazine of the American Chemical Society, explores what else is in the works.

Melody M. Bomgardner, a senior editor at C&EN [Chemical & Engineering News], notes that compared to traditional biotechnology, CRISPR allows scientists to add and remove specific genes from organisms with greater speed, precision and oftentimes, at a lower cost. Among other things, it could potentially lead to higher quality cotton, non-browning mushrooms, drought-resistant corn and — finally — tasty, grocery store tomatoes.

Some hurdles remain, however, before more CRISPR products become available. Regulators are assessing how they should approach crops modified with the technique, which often (though not always) splices genes into a plant from within the species rather than introducing a foreign gene. And scientists still don’t understand all the genes in any given crop, much less know which ones might be good candidates for editing. Luckily, researchers can use CRISPR to find out.

Melody M. Bomgardner’s June 12, 2017 article for C&EN describes in detail how CRISPR could significantly change agriculture (Note: Links have been removed),

When the seed firm DuPont Pioneer first announced the new corn in early 2016, few people paid attention. Pharmaceutical companies using CRISPR for new drugs got the headlines instead.

But people should notice DuPont’s waxy corn because using CRISPR—an acronym for clustered regularly interspaced short palindromic repeats—to delete or alter traits in plants is changing the world of plant breeding, scientists say. Moreover, the technique’s application in agriculture is likely to reach the public years before CRISPR-aided drugs hit the market.

Until CRISPR tools were developed, the process of finding useful traits and getting them into reliable, productive plants took many years. It involved a lot of steps and was plagued by randomness.

“Now, because of basic research in the lab and in the field, we can go straight after the traits we want,” says Zachary Lippman, professor of biological sciences at Cold Spring Harbor Laboratory. CRISPR has been transformative, Lippman says. “It’s basically a freight train that’s not going to stop.”

Proponents hope consumers will embrace gene-edited crops in a way that they did not accept genetically engineered ones, especially because they needn’t involve the introduction of genes from other species—a process that gave rise to the specter of Frankenfood.

But it’s not clear how consumers will react or if gene editing will result in traits that consumers value. And the potential commercial uses of CRISPR may narrow if agriculture agencies in the U.S. and Europe decide to regulate gene-edited crops in the same way they do genetically engineered crops.

DuPont Pioneer expects the U.S. to treat its gene-edited waxy corn like a conventional crop because it does not contain any foreign genes, according to Neal Gutterson, the company’s vice president of R&D. In fact, the waxy trait already exists in some corn varieties. It gives the kernels a starch content of more than 97% amylopectin, compared with 75% amylopectin in regular feed corn. The rest of the kernel is amylose. Amylopectin is more soluble than amylose, making starch from waxy corn a better choice for paper adhesives and food thickeners.

Like most of today’s crops, DuPont’s current waxy corn varieties are the result of decades of effort by plant breeders using conventional breeding techniques.

Breeders identify new traits by examining unusual, or mutant, plants. Over many generations of breeding, they work to get a desired trait into high-performing (elite) varieties that lack the trait. They begin with a first-generation cross, or hybrid, of a mutant and an elite plant and then breed several generations of hybrids with the elite parent in a process called backcrossing. They aim to achieve a plant that best approximates the elite version with the new trait.

But it’s tough to grab only the desired trait from a mutant and make a clean getaway. DuPont’s plant scientists found that the waxy trait came with some genetic baggage; even after backcrossing, the waxy corn plant did not offer the same yield as elite versions without the trait. The disappointing outcome is common enough that it has its own term: yield drag.

Because the waxy trait is native to certain corn plants, DuPont did not have to rely on the genetic engineering techniques that breeders have used to make herbicide-tolerant and insect-resistant corn plants. Those commonly planted crops contain DNA from other species.

In addition to giving some consumers pause, that process does not precisely place the DNA into the host plant. So researchers must raise hundreds or thousands of modified plants to find the best ones with the desired trait and work to get that trait into each elite variety. Finally, plants modified with traditional genetic engineering need regulatory approval in the U.S. and other countries before they can be marketed.

Instead, DuPont plant scientists used CRISPR to zero in on, and partially knock out, a gene for an enzyme that produces amylose. By editing the gene directly, they created a waxy version of the elite corn without yield drag or foreign DNA.

Plant scientists who adopt gene editing may still need to breed, measure, and observe because traits might not work well together or bring a meaningful benefit. “It’s not a panacea,” Lippman says, “but it is one of the most powerful tools to come around, ever.”

It’s an interesting piece which answers the question of why tomatoes from the grocery store don’t taste good.

CRISPR and editing the germline in the US (part 3 of 3): public discussions and pop culture

After giving a basic explanation of the technology and some of the controversies in part 1 and offering more detail about the technology and about the possibility of designer babies in part 2; this part covers public discussion, a call for one and the suggestion that one is taking place in popular culture.

But a discussion does need to happen

In a move that is either an exquisite coincidence or has been carefully orchestrated (I vote for the latter), researchers from the University of Wisconsin-Madison have released a study about attitudes in the US to human genome editing. From an Aug. 11, 2017 University of Wisconsin-Madison news release (also on EurekAllert),

In early August 2017, an international team of scientists announced they had successfully edited the DNA of human embryos. As people process the political, moral and regulatory issues of the technology — which nudges us closer to nonfiction than science fiction — researchers at the University of Wisconsin-Madison and Temple University show the time is now to involve the American public in discussions about human genome editing.

In a study published Aug. 11 in the journal Science, the researchers assessed what people in the United States think about the uses of human genome editing and how their attitudes may drive public discussion. They found a public divided on its uses but united in the importance of moving conversations forward.

“There are several pathways we can go down with gene editing,” says UW-Madison’s Dietram Scheufele, lead author of the study and member of a National Academy of Sciences committee that compiled a report focused on human gene editing earlier this year. “Our study takes an exhaustive look at all of those possible pathways forward and asks where the public stands on each one of them.”

Compared to previous studies on public attitudes about the technology, the new study takes a more nuanced approach, examining public opinion about the use of gene editing for disease therapy versus for human enhancement, and about editing that becomes hereditary versus editing that does not.

The research team, which included Scheufele and Dominique Brossard — both professors of life sciences communication — along with Michael Xenos, professor of communication arts, first surveyed study participants about the use of editing to treat disease (therapy) versus for enhancement (creating so-called “designer babies”). While about two-thirds of respondents expressed at least some support for therapeutic editing, only one-third expressed support for using the technology for enhancement.

Diving even deeper, researchers looked into public attitudes about gene editing on specific cell types — somatic or germline — either for therapy or enhancement. Somatic cells are non-reproductive, so edits made in those cells do not affect future generations. Germline cells, however, are heritable, and changes made in these cells would be passed on to children.

Public support of therapeutic editing was high both in cells that would be inherited and those that would not, with 65 percent of respondents supporting therapy in germline cells and 64 percent supporting therapy in somatic cells. When considering enhancement editing, however, support depended more upon whether the changes would affect future generations. Only 26 percent of people surveyed supported enhancement editing in heritable germline cells and 39 percent supported enhancement of somatic cells that would not be passed on to children.

“A majority of people are saying that germline enhancement is where the technology crosses that invisible line and becomes unacceptable,” says Scheufele. “When it comes to therapy, the public is more open, and that may partly be reflective of how severe some of those genetically inherited diseases are. The potential treatments for those diseases are something the public at least is willing to consider.”

Beyond questions of support, researchers also wanted to understand what was driving public opinions. They found that two factors were related to respondents’ attitudes toward gene editing as well as their attitudes toward the public’s role in its emergence: the level of religious guidance in their lives, and factual knowledge about the technology.

Those with a high level of religious guidance in their daily lives had lower support for human genome editing than those with low religious guidance. Additionally, those with high knowledge of the technology were more supportive of it than those with less knowledge.

While respondents with high religious guidance and those with high knowledge differed on their support for the technology, both groups highly supported public engagement in its development and use. These results suggest broad agreement that the public should be involved in questions of political, regulatory and moral aspects of human genome editing.

“The public may be split along lines of religiosity or knowledge with regard to what they think about the technology and scientific community, but they are united in the idea that this is an issue that requires public involvement,” says Scheufele. “Our findings show very nicely that the public is ready for these discussions and that the time to have the discussions is now, before the science is fully ready and while we have time to carefully think through different options regarding how we want to move forward.”

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

U.S. attitudes on human genome editing by Dietram A. Scheufele, Michael A. Xenos, Emily L. Howell, Kathleen M. Rose, Dominique Brossard1, and Bruce W. Hardy. Science 11 Aug 2017: Vol. 357, Issue 6351, pp. 553-554 DOI: 10.1126/science.aan3708

This paper is behind a paywall.

A couple of final comments

Briefly, I notice that there’s no mention of the ethics of patenting this technology in the news release about the study.

Moving on, it seems surprising that the first team to engage in germline editing in the US is in Oregon; I would have expected the work to come from Massachusetts, California, or Illinois where a lot of bleeding edge medical research is performed. However, given the dearth of financial support from federal funding institutions, it seems likely that only an outsider would dare to engage i the research. Given the timing, Mitalipov’s work was already well underway before the recent about-face from the US National Academy of Sciences (Note: Kaiser’s Feb. 14, 2017 article does note that for some the recent recommendations do not represent any change).

As for discussion on issues such as editing of the germline, I’ve often noted here that popular culture (including advertising with the science fiction and other dramas laid in various media) often provides an informal forum for discussion. Joelle Renstrom in an Aug. 13, 2017 article for slate.com writes that Orphan Black (a BBC America series featuring clones) opened up a series of questions about science and ethics in the guise of a thriller about clones. She offers a précis of the first four seasons (Note: A link has been removed),

If you stopped watching a few seasons back, here’s a brief synopsis of how the mysteries wrap up. Neolution, an organization that seeks to control human evolution through genetic modification, began Project Leda, the cloning program, for two primary reasons: to see whether they could and to experiment with mutations that might allow people (i.e., themselves) to live longer. Neolution partnered with biotech companies such as Dyad, using its big pharma reach and deep pockets to harvest people’s genetic information and to conduct individual and germline (that is, genetic alterations passed down through generations) experiments, including infertility treatments that result in horrifying birth defects and body modification, such as tail-growing.

She then provides the article’s thesis (Note: Links have been removed),

Orphan Black demonstrates Carl Sagan’s warning of a time when “awesome technological powers are in the hands of a very few.” Neolutionists do whatever they want, pausing only to consider whether they’re missing an opportunity to exploit. Their hubris is straight out of Victor Frankenstein’s playbook. Frankenstein wonders whether he ought to first reanimate something “of simpler organisation” than a human, but starting small means waiting for glory. Orphan Black’s evil scientists embody this belief: if they’re going to play God, then they’ll control not just their own destinies, but the clones’ and, ultimately, all of humanity’s. Any sacrifices along the way are for the greater good—reasoning that culminates in Westmoreland’s eugenics fantasy to genetically sterilize 99 percent of the population he doesn’t enhance.

Orphan Black uses sci-fi tropes to explore real-world plausibility. Neolution shares similarities with transhumanism, the belief that humans should use science and technology to take control of their own evolution. While some transhumanists dabble in body modifications, such as microchip implants or night-vision eye drops, others seek to end suffering by curing human illness and aging. But even these goals can be seen as selfish, as access to disease-eradicating or life-extending technologies would be limited to the wealthy. Westmoreland’s goal to “sell Neolution to the 1 percent” seems frighteningly plausible—transhumanists, who statistically tend to be white, well-educated, and male, and their associated organizations raise and spend massive sums of money to help fulfill their goals. …

On Orphan Black, denial of choice is tantamount to imprisonment. That the clones have to earn autonomy underscores the need for ethics in science, especially when it comes to genetics. The show’s message here is timely given the rise of gene-editing techniques such as CRISPR. Recently, the National Academy of Sciences gave germline gene editing the green light, just one year after academy scientists from around the world argued it would be “irresponsible to proceed” without further exploring the implications. Scientists in the United Kingdom and China have already begun human genetic engineering and American scientists recently genetically engineered a human embryo for the first time. The possibility of Project Leda isn’t farfetched. Orphan Black warns us that money, power, and fear of death can corrupt both people and science. Once that happens, loss of humanity—of both the scientists and the subjects—is inevitable.

In Carl Sagan’s dark vision of the future, “people have lost the ability to set their own agendas or knowledgeably question those in authority.” This describes the plight of the clones at the outset of Orphan Black, but as the series continues, they challenge this paradigm by approaching science and scientists with skepticism, ingenuity, and grit. …

I hope there are discussions such as those Scheufele and Brossard are advocating but it might be worth considering that there is already some discussion underway, as informal as it is.

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Part 1: CRISPR and editing the germline in the US (part 1 of 3): In the beginning

Part 2: CRISPR and editing the germline in the US (part 2 of 3): ‘designer babies’?