Tag Archives: CRISPR/Cas9

Precision targeting of the liver for gene editing

Apparently the magic is in the lipid nanoparticles. A March 1, 2021 news item on Nanowerk announced research into lipid nanoparticles as a means to deliver CRISPR (clustered regularly interspaced short palindromic repeats) to specific organs (Note: A link has been removed),

The genome editing technology CRISPR has emerged as a powerful new tool that can change the way we treat disease. The challenge when altering the genetics of our cells, however, is how to do it safely, effectively, and specifically targeted to the gene, tissue and organ that needs treatment.

Scientists at Tufts University and the Broad Institute of Harvard [University] and MIT [Massachusetts Institute of Technology] have developed unique nanoparticles comprised of lipids — fat molecules — that can package and deliver gene editing machinery specifically to the liver.

In a study published in the Proceedings of the National Academy of Sciences [PNAS] (“Lipid nanoparticle-mediated codelivery of Cas9 mRNA and single-guide RNA achieves liver-specific in vivo genome editing of Angptl3”), they have shown that they can use the lipid nanoparticles (LNPs) to efficiently deliver the CRISPR machinery into the liver of mice, resulting in specific genome editing and the reduction of blood cholesterol levels by as much as 57% — a reduction that can last for at least several months with just one shot.

A March 2, 2021 Tufts University news release (also on EurekAlert but published March 1, 2021), which originated the news item, provides greater insight into and technical detail about the research,

The problem of high cholesterol plagues more than 29 million Americans, according to the Centers for Disease Control and Prevention. The condition is complex and can originate from multiple genes as well as nutritional and lifestyle choices, so it is not easy to treat. The Tufts and Broad researchers, however, have modified one gene that could provide a protective effect against elevated cholesterol if it can be shut down by gene editing.

The gene that the researchers focused on codes for the angiopoietin-like 3 enzyme (Angptl3). That enzyme tamps down the activity of other enzymes – lipases – that help break down cholesterol. If researchers can knock out the Angptl3 gene, they can let the lipases do their work and reduce levels of cholesterol in the blood. It turns out that some lucky people have a natural mutation in their Angptl3 gene, leading to consistently low levels of triglycerides and low-density lipoprotein (LDL) cholesterol, commonly called “bad” cholesterol, in their bloodstream without any known clinical downsides.

“If we can replicate that condition by knocking out the angptl3 gene in others, we have a good chance of having a safe and long term solution to high cholesterol,” said Qiaobing Xu, associate professor of biomedical engineering at Tufts’ School of Engineering and corresponding author of the study. “We just have to make sure we deliver the gene editing package specifically to the liver so as not to create unwanted side effects.”

Xu’s team was able to do precisely that in mouse models. After a single injection of lipid nanoparticles packed with mRNA coding for CRISPR-Cas9 and a single-guide RNA targeting Angptl3, they observed a profound reduction in LDL cholesterol by as much as 57% and triglyceride levels by about 29 %, both of which remained at those lowered levels for at least 100 days. The researchers speculate that the effect may last much longer than that, perhaps limited only by the slow turnover of cells in the liver, which can occur over a period of about a year. The reduction of cholesterol and triglycerides is dose dependent, so their levels could be adjusted by injecting fewer or more LNPs in the single shot, the researchers said.

By comparison, an existing, FDA [US Food and Drug Administration]-approved version of CRISPR mRNA-loaded LNPs could only reduce LDL cholesterol by at most 15.7% and triglycerides by 16.3% when it was tested in mice, according to the researchers.

The trick to making a better LNP was in customizing the components – the molecules that come together to form bubbles around the mRNA. The LNPs are made up of long chain lipids that have a charged or polar head that is attracted to water, a carbon chain tail that points toward the middle of the bubble containing the payload, and a chemical linker between them. Also present are polyethylene glycol, and yes, even some cholesterol – which has a normal role in lipid membranes to make them less leaky – to hold their contents better.

The researchers found that the nature and relative ratio of these components appeared to have profound effects on the delivery of mRNA into the liver, so they tested LNPs with many combinations of heads, tails, linkers and ratios among all components for their ability to target liver cells. Because the in vitro potency of an LNP formulation rarely reflects its in vivo performance, they directly evaluated the delivery specificity and efficacy in mice that have a reporter gene in their cells that lights up red when genome editing occurs. Ultimately, they found a CRISPR mRNA-loaded LNP that lit up just the liver in mice, showing that it could specifically and efficiently deliver gene-editing tools into the liver to do their work.

The LNPs were built upon earlier work at Tufts, where Xu and his team developed LNPs with as much as 90% efficiency in delivering mRNA into cells. A unique feature of those nanoparticles was the presence of disulfide bonds between the long lipid chains. Outside the cells, the LNPs form a stable spherical structure that locks in their contents. When they are inside a cell, the environment within breaks the disulfide bonds to disassemble the nanoparticles. The contents are then quickly and efficiently released into the cell. By preventing loss outside the cell, the LNPs can have a much higher yield in delivering their contents.

“CRISPR is one of the most powerful therapeutic tools for the treatment of diseases with a genetic etiology. We have recently seen the first human clinical trail for CRISPR therapy enabled by LNP delivery to be administered systemically to edit genes inside the human body. Our LNP platform developed here holds great potential for clinical translation,” said Min Qiu, post-doctoral researcher in Xu’s lab at Tufts.  “We envision that with this LNP platform in hand, we could now make CRISPR a practical and safe approach to treat a broad spectrum of liver diseases or disorders,” said Zachary Glass, graduate student in the Xu lab. Qiu and Glass are co-first authors of the study.

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

Lipid nanoparticle-mediated codelivery of Cas9 mRNA and single-guide RNA achieves liver-specific in vivo genome editing of Angptl3 by Min Qiu, Zachary Glass, Jinjin Chen, Mary Haas, Xin Jin, Xuewei Zhao, Xuehui Rui, Zhongfeng Ye, Yamin Li, Feng Zhang, and Qiaobing Xu. PNAS March 9, 2021 118 (10) e2020401118 DOI: https://doi.org/10.1073/pnas.2020401118

This paper appears to be behind a paywall.

CRISPR/Cas9 used successfully to edit SIV (simian immunodeficiency virus, which is similar to HIV) out of monkey genome

Before reading further please note, the research discussed in this posting is based on animal testing, which many people find highly disturbing.

CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9), or more familiarly CRISPR/Cas9, has been been used to edit simian immunodeficiency virus from infected monkeys’ cells according to a December 2, 2020 article by Matthew Rozsa for Salon.com (Note: Links have been removed),

With multiple coronavirus vaccines being produced as we speak, the COVID-19 pandemic appears to have an end in sight, though the HIV pandemic continues after more than 40 years. That might seem like a head-scratcher: why is HIV, a virus we’ve known about for decades, so much harder to cure than a virus discovered just last year? Part of the reason is that HIV, as a retrovirus, is a more complex virus to vaccinate against than SARS-CoV-2 — hence why a vaccine or other cure has eluded scientists for decades. 

Now, a surprising new study on a related retrovirus shows incredible promise for the potential to develop a cure for HIV, or human immunodeficiency virus. In an article published in the scientific journal Nature Communications, scientists revealed that they had used CRISPR – a genetic technology that can alter DNA and whose developers won the 2020 Nobel Prize in Chemistry [specifically, Jennifer Doudna and Emanuelle Charpentier received the Nobel for developing CRISPR-cas9 or CRISPR/Cas9 not CRISPR alone) — to successfully edit SIV (simian immunodeficiency virus), a virus similar to HIV, out of the genomes of non-human primates.  Specifically, the scientists were able to edit out the SIV genome from rhesus macaque monkeys’ infected cells.

For anyone who’s interested in how CRISPR was developed and the many contributions which have led to the current state-of-the-art for CRISPR gene editing, see the History subsection of Wikipedia’s CRISPR entry.

Getting back to Rozsa’s December 2, 2020 article,

“This study used the CRISPR CaS9 system, which has been described as molecular scissors,” Andrew G. MacLean, PhD, wrote to Salon. MacLean is an associate professor at the Tulane National Primate Research Center and the Department of Microbiology and Immunology at Tulane University School of Medicine and was a senior co-investigator of the study. “It uses a highly specific targeting system to cut out a specific portion of DNA that is necessary for HIV to be able to produce more virus.”

He added, “Our collaborators at in the Khalili Lab at Temple University have developed a method of ‘packaging’ this within a single so-called vector. A vector is a non-disease causing virus that is used as a carrier for the CRISPR CaS9 scissors to get it into the tissues of interest.”

The experiments with SIV are considered to be a gateway to understanding HIV, as HIV is believed to have evolved from SIV, and is genetically similar.

“The rhesus macaque model of HIV/AIDS is the most valuable model to test efficacy of new interventions or approaches for preventing or treating HIV infection, prior to human clinical trials,” Binhua Ling, PhD, associate professor at the Southwest National Primate Research Center, Texas Biomedical Research Institute, wrote to Salon. “This first proof-of-principal [emphasis mine] study on the rhesus macaque model indicates that this virus-vehicle-delivered-CRISPR system can reach many tissue sites of the body, and is able to effectively delete virus DNA in infected cells. This paves the way for applying the same technology to the human body, which could lead to a cure for HIV infection.”

Tricia H. Burdo, PhD, another senior co-investigator on the new study who works at the Lewis Katz School of Medicine at Temple University, explained to Salon by email that “HIV is in a class of viruses (retroviruses) that inserts itself into the DNA of the host, so you can really think of this now as a genetic disease” — in other words, the kind of thing that would be ripe for CRISPR’s scissors-like ability to remove errant or unwanted genetic material. Burdo notes that the CRISPR technology discussed in the article “cuts out this foreign viral gene.”

The study was conducted on eight Rhesus macaque monkeys. That is a very small number to start with and not all of the monkeys received the CRISPR/Cas9 treatment. From the ‘Animals used in the study and ethical statement‘ subsection of the study, “Animals were sacrificed for tissue collection 3 weeks after … .” Leaving aside how anyone may feel about ‘sacrificing …’, three weeks is not a long time for observation.

Should you be interested, there is a November 30, 2020 Tulane University news release announcing the research.

If you want to read the whole study, here’s a link and a citation,

CRISPR based editing of SIV proviral DNA in ART treated non-human primates by Pietro Mancuso, Chen Chen, Rafal Kaminski, Jennifer Gordon, Shuren Liao, Jake A. Robinson, Mandy D. Smith, Hong Liu, Ilker K. Sariyer, Rahsan Sariyer, Tiffany A. Peterson, Martina Donadoni, Jaclyn B. Williams, Summer Siddiqui, Bruce A. Bunnell, Binhua Ling, Andrew G. MacLean, Tricia H. Burdo & Kamel Khalili. Nature Communications volume 11, Article number: 6065 (2020) DOI: https://doi.org/10.1038/s41467-020-19821-7 Published: 27 November 2020

This paper is open access.

As Rozsa notes in his December 2, 2020 article, the Joint United Nations Programme on HIV/AIDS estimates that 32.7 million [24.8 million–42.2 million] people have died from AIDS-related illnesses since the start (1981?) of the epidemic to the end of 2019.

Xenotransplantation—organs for transplantation in human patients—it’s a business and a science

The last time (June 18, 2018 post) I mentioned xenotransplantation (transplanting organs from one species into another species; see more here), it was in the context of an art/sci (or sciart) event coming to Vancouver (Canada).,

Patricia Piccinini’s Curious Imaginings Courtesy: Vancouver Biennale [downloaded from http://dailyhive.com/vancouver/vancouver-biennale-unsual-public-art-2018/]

The latest edition of the Vancouver Biennale was featured in a June 6, 2018 news item on the Daily Hive (Vancouver),

Melbourne artist Patricia Piccinini’s Curious Imaginings is expected to be one of the most talked about installations of the exhibit. Her style of “oddly captivating, somewhat grotesque, human-animal hybrid creature” is meant to be shocking and thought-provoking.

Piccinini’s interactive [emphasis mine] experience will “challenge us to explore the social impacts of emerging biotechnology and our ethical limits in an age where genetic engineering and digital technologies are already pushing the boundaries of humanity.”

Piccinini’s work will be displayed in the 105-year-old Patricia Hotel in Vancouver’s Strathcona neighbourhood. The 90-day ticketed exhibition [emphasis mine] is scheduled to open this September [2018].

(The show opens on Sept. 14, 2018.)

At the time, I had yet to stumble across Ingfei Chen’s thoughtful dive into the topic in her May 9, 2018 article for Slate.com,

In the United States, the clock is ticking for more than 114,700 adults and children waiting for a donated kidney or other lifesaving organ, and each day, nearly 20 of them die. Researchers are devising a new way to grow human organs inside other animals, but the method raises potentially thorny ethical issues. Other conceivable futuristic techniques sound like dystopian science fiction. As we envision an era of regenerative medicine decades from now, how far is society willing to go to solve the organ shortage crisis?

I found myself pondering this question after a discussion about the promises of stem cell technologies veered from the intriguing into the bizarre. I was interviewing bioengineer Zev Gartner, co-director and research coordinator of the Center for Cellular Construction at the University of California, San Francisco, about so-called organoids, tiny clumps of organlike tissue that can self-assemble from human stem cells in a Petri dish. These tissue bits are lending new insights into how our organs form and diseases take root. Some researchers even hope they can nurture organoids into full-size human kidneys, pancreases, and other organs for transplantation.

Certain organoid experiments have recently set off alarm bells, but when I asked Gartner about it, his radar for moral concerns was focused elsewhere. For him, the “really, really thought-provoking” scenarios involve other emerging stem cell–based techniques for engineering replacement organs for people, he told me. “Like blastocyst complementation,” he said.

Never heard of it? Neither had I. Turns out it’s a powerful new genetic engineering trick that researchers hope to use for growing human organs inside pigs or sheep—organs that could be genetically personalized for transplant patients, in theory avoiding immune-system rejection problems. The science still has many years to go, but if it pans out, it could be one solution to the organ shortage crisis. However, the prospect of creating hybrid animals with human parts and killing them to harvest organs has already raised a slew of ethical questions. In 2015, the National Institutes of Health placed a moratorium on federal funding of this nascent research area while it evaluated and discussed the issues.

As Gartner sees it, the debate over blastocyst complementation research—work that he finds promising—is just one of many conversations that society needs to have about the ethical and social costs and benefits of future technologies for making lifesaving transplant organs. “There’s all these weird ways that we could go about doing this,” he said, with a spectrum of imaginable approaches that includes organoids, interspecies organ farming, and building organs from scratch using 3D bioprinters. But even if it turns out we can produce human organs in these novel ways, the bigger issue, in each technological instance, may be whether we should.

Gartner crystallized things with a downright creepy example: “We know that the best bioreactor for tissues and organs for humans are human beings,” he said. Hypothetically, “the best way to get you a new heart would be to clone you, grow up a copy of yourself, and take the heart out.” [emphasis mine] Scientists could probably produce a cloned person with the technologies we already have, if money and ethics were of no concern. “But we don’t want to go there, right?” he added in the next breath. “The ethics involved in doing it are not compatible with who we want to be as a society.”

This sounds like Gartner may have been reading some science fiction, specifically, Lois McMaster Bujold and her Barrayar series where she often explored the ethics and possibilities of bioengineering. At this point, some of her work seems eerily prescient.

As for Chen’s article, I strongly encourage you to read it in its entirety if you have the time.

Medicine, healing, and big money

At about the same time, there was a May 31, 2018 news item on phys.org offering a perspective from some of the leaders in the science and the business (Note: Links have been removed),

Over the past few years, researchers led by George Church have made important strides toward engineering the genomes of pigs to make their cells compatible with the human body. So many think that it’s possible that, with the help of CRISPR technology, a healthy heart for a patient in desperate need might one day come from a pig.

“It’s relatively feasible to change one gene in a pig, but to change many dozens—which is quite clear is the minimum here—benefits from CRISPR,” an acronym for clustered regularly interspaced short palindromic repeats, said Church, the Robert Winthrop Professor of Genetics at Harvard Medical School (HMS) and a core faculty member of Harvard’s Wyss Institute for Biologically Inspired Engineering. Xenotransplantation is “one of few” big challenges (along with gene drives and de-extinction, he said) “that really requires the ‘oomph’ of CRISPR.”

To facilitate the development of safe and effective cells, tissues, and organs for future medical transplantation into human patients, Harvard’s Office of Technology Development has granted a technology license to the Cambridge biotech startup eGenesis.

Co-founded by Church and former HMS doctoral student Luhan Yang in 2015, eGenesis announced last year that it had raised $38 million to advance its research and development work. At least eight former members of the Church lab—interns, doctoral students, postdocs, and visiting researchers—have continued their scientific careers as employees there.

“The Church Lab is well known for its relentless pursuit of scientific achievements so ambitious they seem improbable—and, indeed, [for] its track record of success,” said Isaac Kohlberg, Harvard’s chief technology development officer and senior associate provost. “George deserves recognition too for his ability to inspire passion and cultivate a strong entrepreneurial drive among his talented research team.”

The license from Harvard OTD covers a powerful set of genome-engineering technologies developed at HMS and the Wyss Institute, including access to foundational intellectual property relating to the Church Lab’s 2012 breakthrough use of CRISPR, led by Yang and Prashant Mali, to edit the genome of human cells. Subsequent innovations that enabled efficient and accurate editing of numerous genes simultaneously are also included. The license is exclusive to eGenesis but limited to the field of xenotransplantation.

A May 30, 2018 Harvard University news release by Caroline Petty, which originated the news item, explores some of the issues associated with incubating humans organs in other species,

The prospect of using living, nonhuman organs, and concerns over the infectiousness of pathogens either present in the tissues or possibly formed in combination with human genetic material, have prompted the Food and Drug Administration to issue detailed guidance on xenotransplantation research and development since the mid-1990s. In pigs, a primary concern has been that porcine endogenous retroviruses (PERVs), strands of potentially pathogenic DNA in the animals’ genomes, might infect human patients and eventually cause disease. [emphases mine]

That’s where the Church lab’s CRISPR expertise has enabled significant advances. In 2015, the lab published important results in the journal Science, successfully demonstrating the use of genome engineering to eliminate all 62 PERVs in porcine cells. Science later called it “the most widespread CRISPR editing feat to date.”

In 2017, with collaborators at Harvard, other universities, and eGenesis, Church and Yang went further. Publishing again in Science, they first confirmed earlier researchers’ fears: Porcine cells can, in fact, transmit PERVs into human cells, and those human cells can pass them on to other, unexposed human cells. (It is still unknown under what circumstances those PERVs might cause disease.) In the same paper, they corrected the problem, announcing the embryogenesis and birth of 37 PERV-free pigs. [Note: My July 17, 2018 post features research which suggests CRISPR-Cas9 gene editing may cause greater genetic damage than had been thought.]

“Taken together, those innovations were stunning,” said Vivian Berlin, director of business development in OTD, who manages the commercialization strategy for much of Harvard’s intellectual property in the life sciences. “That was the foundation they needed, to convince both the scientific community and the investment community that xenotransplantation might become a reality.”

“After hundreds of tests, this was a critical milestone for eGenesis — and the entire field — and represented a key step toward safe organ transplantation from pigs,” said Julie Sunderland, interim CEO of eGenesis. “Building on this study, we hope to continue to advance the science and potential of making xenotransplantation a safe and routine medical procedure.”

Genetic engineering may undercut human diseases, but also could help restore extinct species, researcher says. [Shades of the Jurassic Park movies!]

It’s not, however, the end of the story: An immunological challenge remains, which eGenesis will need to address. The potential for a patient’s body to outright reject transplanted tissue has stymied many previous attempts at xenotransplantation. Church said numerous genetic changes must be achieved to make porcine organs fully compatible with human patients. Among these are edits to several immune functions, coagulation functions, complements, and sugars, as well as the PERVs.

“Trying the straight transplant failed almost immediately, within hours, because there’s a huge mismatch in the carbohydrates on the surface of the cells, in particular alpha-1-3-galactose, and so that was a showstopper,” Church explained. “When you delete that gene, which you can do with conventional methods, you still get pretty fast rejection, because there are a lot of other aspects that are incompatible. You have to take care of each of them, and not all of them are just about removing things — some of them you have to humanize. There’s a great deal of subtlety involved so that you get normal pig embryogenesis but not rejection.

“Putting it all together into one package is challenging,” he concluded.

In short, it’s the next big challenge for CRISPR.

Not unexpectedly, there is no mention of the CRISPR patent fight between Harvard/MIT’s (Massachusetts Institute of Technology) Broad Institute and the University of California at Berkeley (UC Berkeley). My March 15, 2017 posting featured an outcome where the Broad Institute won the first round of the fight. As I recall, it was a decision based on the principles associated with King Solomon, i.e., the US Patent Office, divided the baby and UCBerkeley got the less important part of the baby. As you might expect the decision has been appealed. In an April 30, 2018 piece, Scientific American reprinted an article about the latest round in the fight written by Sharon Begley for STAT (Note: Links have been removed),

All You Need to Know for Round 2 of the CRISPR Patent Fight

It’s baaaaack, that reputation-shredding, stock-moving fight to the death over key CRISPR patents. On Monday morning in Washington, D.C., the U.S. Court of Appeals for the Federal Circuit will hear oral arguments in University of California v. Broad Institute. Questions?

How did we get here? The patent office ruled in February 2017 that the Broad’s 2014 CRISPR patent on using CRISPR-Cas9 to edit genomes, based on discoveries by Feng Zhang, did not “interfere” with a patent application by UC based on the work of UC Berkeley’s Jennifer Doudna. In plain English, that meant the Broad’s patent, on using CRISPR-Cas9 to edit genomes in eukaryotic cells (all animals and plants, but not bacteria), was different from UC’s, which described Doudna’s experiments using CRISPR-Cas9 to edit DNA in a test tube—and it was therefore valid. The Patent Trial and Appeal Board concluded that when Zhang got CRISPR-Cas9 to work in human and mouse cells in 2012, it was not an obvious extension of Doudna’s earlier research, and that he had no “reasonable expectation of success.” UC appealed, and here we are.

For anyone who may not realize what the stakes are for these institutions, Linda Williams in a March 16, 1999 article for the LA Times had this to say about universities, patents, and money,

The University of Florida made about $2 million last year in royalties on a patent for Gatorade Thirst Quencher, a sports drink that generates some $500 million to $600 million a year in revenue for Quaker Oats Co.

The payments place the university among the top five in the nation in income from patent royalties.

Oh, but if some people on the Gainesville, Fla., campus could just turn back the clock. “If we had done Gatorade right, we would be getting $5 or $6 million (a year),” laments Donald Price, director of the university’s office of corporate programs. “It is a classic example of how not to handle a patent idea,” he added.

Gatorade was developed in 1965 when many universities were ill equipped to judge the commercial potential of ideas emerging from their research labs. Officials blew the university’s chance to control the Gatorade royalties when they declined to develop a professor’s idea.

The Gatorade story does not stop there and, even though it’s almost 20 years old, this article stands the test of time. I strongly encourage you to read it if the business end of patents and academia interest you or if you would like to develop more insight into the Broad Institute/UC Berkeley situation.

Getting back to the science, there is that pesky matter of diseases crossing over from one species to another. While, Harvard and eGenesis claim a victory in this area, it seems more work needs to be done.

Infections from pigs

An August 29, 2018 University of Alabama at Birmingham news release (also on EurekAlert) by Jeff Hansen, describes the latest chapter in the quest to provide more organs for transplantion,

A shortage of organs for transplantation — including kidneys and hearts — means that many patients die while still on waiting lists. So, research at the University of Alabama at Birmingham and other sites has turned to pig organs as an alternative. [emphasis mine]

Using gene-editing, researchers have modified such organs to prevent rejection, and research with primates shows the modified pig organs are well-tolerated.

An added step is needed to ensure the safety of these inter-species transplants — sensitive, quantitative assays for viruses and other infectious microorganisms in donor pigs that potentially could gain access to humans during transplantation.

The U.S. Food and Drug Administration requires such testing, prior to implantation, of tissues used for xenotransplantation from animals to humans. It is possible — though very unlikely — that an infectious agent in transplanted tissues could become an emerging infectious disease in humans.

In a paper published in Xenotransplantation, Mark Prichard, Ph.D., and colleagues at UAB have described the development and testing of 30 quantitative assays for pig infectious agents. These assays had sensitivities similar to clinical lab assays for viral loads in human patients. After validation, the UAB team also used the assays on nine sows and 22 piglets delivered from the sows through caesarian section.

“Going forward, ensuring the safety of these organs is of paramount importance,” Prichard said. “The use of highly sensitive techniques to detect potential pathogens will help to minimize adverse events in xenotransplantation.”

“The assays hold promise as part of the screening program to identify suitable donor animals, validate and release transplantable organs for research purposes, and monitor transplant recipients,” said Prichard, a professor in the UAB Department of Pediatrics and director of the Department of Pediatrics Molecular Diagnostics Laboratory.

The UAB researchers developed quantitative polymerase chain reaction, or qPCR, assays for 28 viruses sometimes found in pigs and two groups of mycoplasmas. They established reproducibility, sensitivity, specificity and lower limit of detection for each assay. All but three showed features of good quantitative assays, and the lower limit of detection values ranged between one and 16 copies of the viral or bacterial genetic material.

Also, the pig virus assays did not give false positives for some closely related human viruses.

As a start to understanding the infectious disease load in normal healthy animals and ensuring the safety of pig tissues used in xenotransplantation research, the researchers then screened blood, nasal swab and stool specimens from nine adult sows and 22 of their piglets delivered by caesarian section.

Mycoplasma species and two distinct herpesviruses were the most commonly detected microorganisms. Yet 14 piglets that were delivered from three sows infected with either or both herpesviruses were not infected with the herpesviruses, showing that transmission of these viruses from sow to the caesarian-delivery piglet was inefficient.

Prichard says the assays promise to enhance the safety of pig tissues for xenotransplantation, and they will also aid evaluation of human specimens after xenotransplantation.

The UAB researchers say they subsequently have evaluated more than 300 additional specimens, and that resulted in the detection of most of the targets. “The detection of these targets in pig specimens provides reassurance that the analytical methods are functioning as designed,” said Prichard, “and there is no a priori reason some targets might be more difficult to detect than others with the methods described here.”

As is my custom, here’s a link to and a citation for the paper,

Xenotransplantation panel for the detection of infectious agents in pigs by Caroll B. Hartline, Ra’Shun L. Conner, Scott H. James, Jennifer Potter, Edward Gray, Jose Estrada, Mathew Tector, A. Joseph Tector, Mark N. Prichard. Xenotransplantaion Volume 25, Issue 4 July/August 2018 e12427 DOI: https://doi.org/10.1111/xen.12427 First published: 18 August 2018

This paper is open access.

All this leads to questions about chimeras. If a pig is incubating organs with human cells it’s a chimera but then means the human receiving the organ becomes a chimera too. (For an example, see my Dec. 22, 2013 posting where there’s mention of a woman who received a trachea from a pig. Scroll down about 30% of the way.)

What is it to be human?

A question much beloved of philosophers and others, the question seems particularly timely with xenotransplantion and other developments such neuroprosthetics (cyborgs) and neuromorphic computing (brainlike computing).

As I’ve noted before, although not recently, popular culture offers a discourse on these issues. Take a look at the superhero movies and the way in which enhanced humans and aliens are presented. For example, X-Men comics and movies present mutants (humans with enhanced abilities) as despised and rejected. Video games (not really my thing but there is the Deus Ex series which has as its hero, a cyborg also offer insight into these issues.

Other than popular culture and in the ‘bleeding edge’ arts community, I can’t recall any public discussion on these matters arising from the extraordinary set of technologies which are being deployed or prepared for deployment in the foreseeable future.

(If you’re in Vancouver (Canada) from September 14 – December 15, 2018, you may want to check out Piccinini’s work. Also, there’s ” NCSU [North Carolina State University] Libraries, NC State’s Genetic Engineering and Society (GES) Center, and the Gregg Museum of Art & Design have issued a public call for art for the upcoming exhibition Art’s Work in the Age of Biotechnology: Shaping our Genetic Futures.” from my Sept. 6, 2018 posting. Deadline: Oct. 1, 2018.)

At a guess, there will be pushback from people who have no interest in debating what it is to be human as they already know, and will find these developments, when they learn about them, to be horrifying and unnatural.

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.