Tag Archives: University of Vienna

Frog pants?

How would you go about tracking these frogs?

Six images of tiny frogs wearing little plastic trackers attached to wire harnesses on their back legs.
Researchers have fitted tiny trackable radio-pants to three species of South American frogs to test their ability to navigate through the rainforest. (Submitted by Andrius Pašukonis)

You can see how tiny they are when you compare one of the frogs to a leaf visible in one of the images (top left or top right).

The answer to the question, as you may have guessed, are frog pants (or G-strings).

Sheena Goodyear’s June 13, 2023 article for the CBC’s (Canadian Broadcasting Corporation) As It Happens radio show explores the question and the research and includes an embedded 6:20 radio interview with researcher, Andrius Pašukonis,

How do you track a bunch of teeny-weeny frogs across the vast rainforests of South America? By putting teeny-weeny trackers on their teeny-weeny underwear, of course.

Biologist Andrius Pašukonis and his colleagues wanted to study the navigational capabilities of poisonous frogs that are too small for most animal tracking devices.

So he designed a Speedo-like harness that wraps around their back legs and props a tiny radio tracker on their backsides. The research team dubbed the invention “frog pants” — though Pašukonis says that’s “a bit of a misnomer.”

“My French colleagues like to call it a telemetric G-string,” Pašukonis, a senior scientist at Lithuania’s Vilnius University, told As It Happens host Nil Köksal.

“It’s a lot of fine motor skills and a lot of practice in handling tiny frogs and sewing little frog harnesses. But we go find them in the rainforest, and we catch them, and we put the tags on.”

My favourite part is “… sewing little frog harnesses.” Note: The following video features a commercial and then, moves onto a 2:22 interview,

More from Goodyear’s June 13, 2023 article, Note: A link has been removed,

Pašukonis was a PhD student at the University of Vienna when he first started experimenting with the frog pants design, and later put it to use while working as a postdoctoral fellow at Stanford University in California.

He and is colleagues used the tracker pants to study the spatial skills of three frog species that range from three to five centimetres in length — diablito poison frogs in Ecuador, and brilliant-thighed poison frogs and dyeing poison frogs in French Guiana. The findings were published late last year in the journal e-Life [sic].

“The only way to study movements of animals is to be able to track them and follow them around, which nobody has managed to do or even tried to do with these tiny, tiny frogs in the rainforest,” he said.

“So that became my goal and challenge, where I spent a good part of my PhD trying different versions of different tags and different attachment methods, trial and error, to finally get to be able to put tags on and track them and study their behaviour.”

The frogs, he admits, didn’t particularly like the pants. But they didn’t seem to mind too much, and the team removed the trackers after four to six days. 

“Like any animal, they might scratch a little bit afterwards … like a dog with a new collar,” he said. “And then they just go on with their business.”

Other scientists have tried to track tiny frogs, from Goodyear’s June 13, 2023 article, Note: Links have been removed,

The design caught the eye of Richard Essner, a biologist at Southern Illinois University Edwardsville who studies animal locomotion, and has a particular interest in little frogs.

“Tracking small frogs with radio telemetry is not an easy thing to do,” Essner, who wasn’t involved in the Stanford research, told CBC in an email. 

About a decade ago, he says his lab attempted to use radio telemetry to track the movement of the threatened Illinois chorus frog using a transmitter attached via an elastic belt around the waist.

“Unfortunately, we had to abandon the study because we found that the transmitter apparatus was interfering with locomotion. If the belt was too tight, it caused abrasion. If it was too loose it slid down around the legs and left the frog immobilized and vulnerable to predation,” he said.

The frog pants, he says, seem to offer a solution to this conundrum. 

Lea Randall, a Calgary Zoo and Wilder Institute ecologist who specializes in amphibians and reptiles, ran into similar obstacles while trying to track northern leopard frogs at a reintroduction site in B.C. 

Like the Stanford researchers, her team experimented with several different designs before landing on one that worked — a belt-like attachment with some “very stylish” smooth glass beads to prevent abrasion. 

“Unfortunately, due to the weight of the radio transmitters at the time we couldn’t study smaller individuals,” she said. 

“We didn’t use leg straps, but I can see the advantages of that to help keep the transmitters in place. The creative thinking and problem solving that goes into developing these kinds of studies always amazes me.”

Finally, frogs may be smarter than we think, from Goodyear’s June 13, 2023 article,

When it comes to animal cognition and behaviour, Pašukonis says frogs are understudied —  and he believes, underestimated — compared to birds and mammals.

The poisonous rainforest frogs, he says, may be only a few centimetres in size, but when they breed, they carry their tadpoles between 200 to 300 metres across the rainforest to find them the perfect puddle to grow in.

Then they turn right around, and make their way home again. 

“How could a little frog — frogs typically are not thought to be very smart — learn to navigate on such a big scale? And how do they find their way around more on a fundamental scientific level?” Pašukonis said.

“We’re uncovering that overall amphibians, for example, might be smarter or have more complicated cognitive abilities than we thought.”

Here’s a link to and a citation for the paper published by Pašukonis and his colleagues,

Contrasting parental roles shape sex differences in poison frog space use but not navigational performance by Andrius Pašukonis, Shirley Jennifer Serrano-Rojas, Marie-Therese Fischer, Matthias-Claudio Loretto, Daniel A Shaykevich, Bibiana Rojas, Max Ringler, Alexandre B Roland, Alejandro Marcillo-Lara, Eva Ringler, Camilo Rodríguez, Luis A Coloma, Lauren A O’Connell. eLife DOI: https://doi.org/10.7554/eLife.80483 Version of Record Published: Nov 15, 2022

This paper appears to be open access.

A CRISPR (clustered regularly interspaced short palindromic repeats) anniversary

June 2022 was the 10th anniversary of the publication of a study the paved the way for CRISPR-Cas9 gene editing and Sophie Fessl’s June 28, 2022 article for The Scientist offers a brief history (Note: Links have been removed),

Ten years ago, Emmanuelle Charpentier and Jennifer Doudna published the study that paved the way for a new kind of genome editing: the suite of technologies now known as CRISPR. Writing in [the journal] Science, they adapted an RNA-mediated bacterial immune defense into a targeted DNA-altering system. “Our study . . . highlights the potential to exploit the system for RNA-programmable genome editing,” they conclude in the abstract of their paper—a potential that, in the intervening years, transformed the life sciences. 

From gene drives to screens, and diagnostics to therapeutics, CRISPR nucleic acids and the Cas enzymes with which they’re frequently paired have revolutionized how scientists tinker with DNA and RNA. … altering the code of life with CRISPR has been marred by ethical concerns. Perhaps the most prominent example was when Chinese scientist He Jiankui created the first gene edited babies using CRISPR/Cas9 genome editing. Doudna condemned Jiankui’s work, for which he was jailed, as “risky and medically unnecessary” and a “shocking reminder of the scientific and ethical challenges raised by this powerful technology.” 

There’s also the fact that legal battles over who gets to claim ownership of the system’s many applications have persisted almost as long as the technology has been around. Both Doudna and Charpentier’s teams from the University of California, Berkeley, and the University of Vienna and a team led by the Broad Institute’s Feng Zhang claim to be the first to have adapted CRISPR-Cas9 for gene editing in complex cells (eukaryotes). Patent offices in different countries have reached varying decisions, but in the US, the latest rulings say that the Broad Institute of MIT [Massachusetts Institute of Technology] and Harvard retains intellectual property of using CRISPR-Cas9 in eukaryotes, while Emmanuelle Charpentier, the University of California, and the University of Vienna maintain their original patent over using CRISPR-Cas9 for editing in vitro and in prokaryotes. 

Still, despite the controversies, the technique continues to be explored academically and commercially for everything from gene therapy to crop improvement. Here’s a look at seven different ways scientists have utilized CRISPR.

Fessl goes on to give a brief overview of CRISPR and gene drives, genetic screens, diagnostics, including COVID-19 tests, gene therapy, therapeutics, crop and livestock improvement, and basic research.

For anyone interested in the ethical issues (with an in depth look at the Dr. He Jiankui story), I suggest reading either or both Eben Kirksey’s 2020 book, “The Mutant Project; Inside the Global Race to Genetically Modify Humans,”

An anthropologist visits the frontiers of genetics, medicine, and technology to ask: Whose values are guiding gene editing experiments? And what does this new era of scientific inquiry mean for the future of the human species?

“That rare kind of scholarship that is also a page-turner.”
—Britt Wray, author of Rise of the Necrofauna

At a conference in Hong Kong in November 2018, Dr. He Jiankui announced that he had created the first genetically modified babies—twin girls named Lulu and Nana—sending shockwaves around the world. A year later, a Chinese court sentenced Dr. He to three years in prison for “illegal medical practice.”

As scientists elsewhere start to catch up with China’s vast genetic research program, gene editing is fueling an innovation economy that threatens to widen racial and economic inequality. Fundamental questions about science, health, and social justice are at stake: Who gets access to gene editing technologies? As countries loosen regulations around the globe, from the U.S. to Indonesia, can we shape research agendas to promote an ethical and fair society?

Eben Kirksey takes us on a groundbreaking journey to meet the key scientists, lobbyists, and entrepreneurs who are bringing cutting-edge genetic engineering tools like CRISPR—created by Nobel Prize-winning biochemists Jennifer Doudna and Emmanuelle Charpentier—to your local clinic. He also ventures beyond the scientific echo chamber, talking to disabled scholars, doctors, hackers, chronically-ill patients, and activists who have alternative visions of a genetically modified future for humanity.

and/or Kevin Davies’s 2020 book, “Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing,”

One of the world’s leading experts on genetics unravels one of the most important breakthroughs in modern science and medicine. 

If our genes are, to a great extent, our destiny, then what would happen if mankind could engineer and alter the very essence of our DNA coding? Millions might be spared the devastating effects of hereditary disease or the challenges of disability, whether it was the pain of sickle-cell anemia to the ravages of Huntington’s disease.

But this power to “play God” also raises major ethical questions and poses threats for potential misuse. For decades, these questions have lived exclusively in the realm of science fiction, but as Kevin Davies powerfully reveals in his new book, this is all about to change.

Engrossing and page-turning, Editing Humanity takes readers inside the fascinating world of a new gene editing technology called CRISPR, a high-powered genetic toolkit that enables scientists to not only engineer but to edit the DNA of any organism down to the individual building blocks of the genetic code.

Davies introduces readers to arguably the most profound scientific breakthrough of our time. He tracks the scientists on the front lines of its research to the patients whose powerful stories bring the narrative movingly to human scale.

Though the birth of the “CRISPR babies” in China made international news, there is much more to the story of CRISPR than headlines seemingly ripped from science fiction. In Editing Humanity, Davies sheds light on the implications that this new technology can have on our everyday lives and in the lives of generations to come.

Kevin Davies is the executive editor of The CRISPR Journal and the founding editor of Nature Genetics. He holds an MA in biochemistry from the University of Oxford and a PhD in molecular genetics from the University of London. He is the author of Cracking the Genome, The $1,000 Genome, and co-authored a new edition of DNA: The Story of the Genetic Revolution with Nobel Laureate James D. Watson and Andrew Berry. In 2017, Kevin was selected for a Guggenheim Fellowship in science writing.

I’ve read both books and while some of the same ground is covered, the perspectives diverge somewhat. Both authors offer a more nuanced discussion of the issues than was the case in the original reporting about Dr. He’s work.

2022 Nobel Prize for Physics winners proved the existence of quantum entanglement

In early October 2022, Alain Aspect, John Clauser and Anton Zeilinger were jointly awarded the 2022 Nobel Prize in Physics for work each scientist performed independently of the others.

Here’s more about the scientists and their works from an October 4, 2022 Nobel Prize press release,

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Physics 2022 to

Alain Aspect
Institut d’Optique Graduate School – Université Paris-
Saclay and École Polytechnique, Palaiseau, France

John F. Clauser
J.F. Clauser & Assoc., Walnut Creek, CA, USA

Anton Zeilinger
University of Vienna, Austria

“for experiments with entangled photons, establishing the violation of Bell inequalities and pioneering quantum information science”

Entangled states – from theory to technology

Alain Aspect, John Clauser and Anton Zeilinger have each conducted groundbreaking experiments using entangled quantum states, where two particles behave like a single unit even when they are separated. Their results have cleared the way for new technology based upon quantum information.

The ineffable effects of quantum mechanics are starting to find applications. There is now a large field of research that includes quantum computers, quantum networks and secure quantum encrypted communication.

One key factor in this development is how quantum mechanics allows two or more particles to exist in what is called an entangled state. What happens to one of the particles in an entangled pair determines what happens to the other particle, even if they are far apart.

For a long time, the question was whether the correlation was because the particles in an entangled pair contained hidden variables, instructions that tell them which result they should give in an experiment. In the 1960s, John Stewart Bell developed the mathematical inequality that is named after him. This states that if there are hidden variables, the correlation between the results of a large number of measurements will never exceed a certain value. However, quantum mechanics predicts that a certain type of experiment will violate Bell’s inequality, thus resulting in a stronger correlation than would otherwise be possible.

John Clauser developed John Bell’s ideas, leading to a practical experiment. When he took the measurements, they supported quantum mechanics by clearly violating a Bell inequality. This means that quantum mechanics cannot be replaced by a theory that uses hidden variables.

Some loopholes remained after John Clauser’s experiment. Alain Aspect developed the setup, using it in a way that closed an important loophole. He was able to switch the measurement settings after an entangled pair had left its source, so the setting that existed when they were emitted could not affect the result.

Using refined tools and long series of experiments, Anton Zeilinger started to use entangled quantum states. Among other things, his research group has demonstrated a phenomenon called quantum teleportation, which makes it possible to move a quantum state from one particle to one at a distance.

“It has become increasingly clear that a new kind of quantum technology is emerging. We can see that the laureates’ work with entangled states is of great importance, even beyond the fundamental questions about the interpretation of quantum mechanics,”says Anders Irbäck, Chair of the Nobel Committee for Physics.

There are some practical applications for their work on establishing quantum entanglement as Dr. Nicholas Peters, University of Tennessee and Oak Ridge National Laboratory (ORNL), explains in his October 7, 2022 essay for The Conversation,

Unhackable communications devices, high-precision GPS and high-resolution medical imaging all have something in common. These technologies—some under development and some already on the market all rely on the non-intuitive quantum phenomenon of entanglement.

Two quantum particles, like pairs of atoms or photons, can become entangled. That means a property of one particle is linked to a property of the other, and a change to one particle instantly affects the other particle, regardless of how far apart they are. This correlation is a key resource in quantum information technologies.

For the most part, quantum entanglement is still a subject of physics research, but it’s also a component of commercially available technologies, and it plays a starring role in the emerging quantum information processing industry.

Quantum entanglement is a critical element of quantum information processing, and photonic entanglement of the type pioneered by the Nobel laureates is crucial for transmitting quantum information. Quantum entanglement can be used to build large-scale quantum communications networks.

On a path toward long-distance quantum networks, Jian-Wei Pan, one of Zeilinger’s former students, and colleagues demonstrated entanglement distribution to two locations separated by 764 miles (1,203 km) on Earth via satellite transmission. However, direct transmission rates of quantum information are limited due to loss, meaning too many photons get absorbed by matter in transit so not enough reach the destination.

Entanglement is critical for solving this roadblock, through the nascent technology of quantum repeaters. An important milestone for early quantum repeaters, called entanglement swapping, was demonstrated by Zeilinger and colleagues in 1998. Entanglement swapping links one each of two pairs of entangled photons, thereby entangling the two initially independent photons, which can be far apart from each other.

Perhaps the most well known quantum communications application is Quantum Key Distribution (QKD), which allows someone to securely distribute encryption keys. If those keys are stored properly, they will be secure, even from future powerful, code-breaking quantum computers.

I don’t usually embed videos that are longer than 5 mins. but this one has a good explanation of cryptography (both classical and quantum),

The video host, Physics Girl (website), is also known as Dianna Cowern.

If you have the time, do read Peters’s October 7, 2022 essay, which can also be found as an October 10, 2022 news item on phys.org.

I wonder if there’s going to be a rush to fund and commercialize more quantum physics projects. There’s certainly an upsurge in activity locally and in Canada (I assume the same is true elsewhere) as my July 26, 2022 posting “Quantum Mechanics & Gravity conference (August 15 – 19, 2022) launches Vancouver (Canada)-based Quantum Gravity Institute and more” makes clear.

Quantum memristors

This March 24, 2022 news item on Nanowerk announcing work on a quantum memristor seems to have had a rough translation from German to English,

In recent years, artificial intelligence has become ubiquitous, with applications such as speech interpretation, image recognition, medical diagnosis, and many more. At the same time, quantum technology has been proven capable of computational power well beyond the reach of even the world’s largest supercomputer.

Physicists at the University of Vienna have now demonstrated a new device, called quantum memristor, which may allow to combine these two worlds, thus unlocking unprecedented capabilities. The experiment, carried out in collaboration with the National Research Council (CNR) and the Politecnico di Milano in Italy, has been realized on an integrated quantum processor operating on single photons.

Caption: Abstract representation of a neural network which is made of photons and has memory capability potentially related to artificial intelligence. Credit: © Equinox Graphics, University of Vienna

A March 24, 2022 University of Vienna (Universität Wien) press release (also on EurekAlert), which originated the news item, explains why this work has an impact on artificial intelligence,

At the heart of all artificial intelligence applications are mathematical models called neural networks. These models are inspired by the biological structure of the human brain, made of interconnected nodes. Just like our brain learns by constantly rearranging the connections between neurons, neural networks can be mathematically trained by tuning their internal structure until they become capable of human-level tasks: recognizing our face, interpreting medical images for diagnosis, even driving our cars. Having integrated devices capable of performing the computations involved in neural networks quickly and efficiently has thus become a major research focus, both academic and industrial.

One of the major game changers in the field was the discovery of the memristor, made in 2008. This device changes its resistance depending on a memory of the past current, hence the name memory-resistor, or memristor. Immediately after its discovery, scientists realized that (among many other applications) the peculiar behavior of memristors was surprisingly similar to that of neural synapses. The memristor has thus become a fundamental building block of neuromorphic architectures.

A group of experimental physicists from the University of Vienna, the National Research Council (CNR) and the Politecnico di Milano led by Prof. Philip Walther and Dr. Roberto Osellame, have now demonstrated that it is possible to engineer a device that has the same behavior as a memristor, while acting on quantum states and being able to encode and transmit quantum information. In other words, a quantum memristor. Realizing such device is challenging because the dynamics of a memristor tends to contradict the typical quantum behavior. 

By using single photons, i.e. single quantum particles of lights, and exploiting their unique ability to propagate simultaneously in a superposition of two or more paths, the physicists have overcome the challenge. In their experiment, single photons propagate along waveguides laser-written on a glass substrate and are guided on a superposition of several paths. One of these paths is used to measure the flux of photons going through the device and this quantity, through a complex electronic feedback scheme, modulates the transmission on the other output, thus achieving the desired memristive behavior. Besides demonstrating the quantum memristor, the researchers have provided simulations showing that optical networks with quantum memristor can be used to learn on both classical and quantum tasks, hinting at the fact that the quantum memristor may be the missing link between artificial intelligence and quantum computing.

“Unlocking the full potential of quantum resources within artificial intelligence is one of the greatest challenges of the current research in quantum physics and computer science”, says Michele Spagnolo, who is first author of the publication in the journal “Nature Photonics”. The group of Philip Walther of the University of Vienna has also recently demonstrated that robots can learn faster when using quantum resources and borrowing schemes from quantum computation. This new achievement represents one more step towards a future where quantum artificial intelligence become reality.

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

Experimental photonic quantum memristor by Michele Spagnolo, Joshua Morris, Simone Piacentini, Michael Antesberger, Francesco Massa, Andrea Crespi, Francesco Ceccarelli, Roberto Osellame & Philip Walther. Nature Photonics volume 16, pages 318–323 (2022) DOI: https://doi.org/10.1038/s41566-022-00973-5 Published 24 March 2022 Issue Date April 2022

This paper is open access.

NanoFARM: food, agriculture, and nanoparticles

The research focus for the NanoFARM consortium is on pesticides according to an October 19, 2017 news item on Nanowerk,

The answer to the growing, worldwide food production problem may have a tiny solution—nanoparticles, which are being explored as both fertilizers and fungicides for crops.

NanoFARM – research consortium formed between Carnegie Mellon University [US], the University of Kentucky [US], the University of Vienna [Austria], and Aveiro University in Prague [Czech Republic] – is studying the effects of nanoparticles on agriculture. The four universities received grants from their countries’ respective National Science Foundations to discover how these tiny particles – some just 4 nanometers in diameter – can revolutionize how farmers grow their food.

An October ??, 2017 Carnegie Mellon University news release by Adam Dove, which originated the news item, fills in a few more details,

“What we’re doing is getting a fundamental understanding of nanoparticle-to-plant interactions to enable future applications,” says Civil and Environmental Engineering (CEE) Professor Greg Lowry, the principal investigator for the nanoFARM project. “With pesticides, less than 5% goes into the crop—the rest just goes into the environment and does harmful things. What we’re trying to do is minimize that waste and corresponding environmental damage by doing a better job of targeting the delivery.”

The teams are looking at related questions: How much nanomaterial is needed to help crops when it comes to driving away pests and delivering nutrients, and how much could potentially hurt plants or surrounding ecosystems?

Applied pesticides and fertilizers are vulnerable to washing away—especially if there’s a rainstorm soon after application. But nanoparticles are not so easily washed off, making them extremely efficient for delivering micronutrients like zinc or copper to crops.

“If you put in zinc oxide nanoparticles instead, it might take days or weeks to dissolve, providing a slow, long-term delivery system.”

Gao researches the rate at which nanoparticles dissolve. His most recent finding is that nanoparticles of copper oxide take up to 20-30 days to dissolve in soil, meaning that they can deliver nutrients to plants at a steady rate over that time period.

“In many developing countries, a huge number of people are starving,” says Gao. “This kind of technology can help provide food and save energy.”

But Gao’s research is only one piece of the NanoFARM puzzle. Lowry recently traveled to Australia with Ph.D. student Eleanor Spielman-Sun to explore how differently charged nanoparticles were absorbed into wheat plants.

They learned that negatively charged particles were able to move into the veins of a plant—making them a good fit for a farmer who wanted to apply a fungicide. Neutrally charged particles went into the tissue of the leaves, which would be beneficial for growers who wanted to fortify a food with nutritional value.

Lowry said they are still a long way from signing off on a finished product for all crops—right now they are concentrating on tomato and wheat plants. But with the help of their university partners, they are slowly creating new nano-enabled agrochemicals for more efficient and environmentally friendly agriculture.

For more information, you can find the NanoFARM website here.

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

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

But a discussion does need to happen

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This paper is behind a paywall.

A couple of final comments

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

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

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

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

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

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

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

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

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

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

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

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

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

Having included an explanation of CRISPR-CAS9 technology along with the news about the first US team to edit the germline and bits and pieces about ethics and a patent fight (part 1), this part hones in on the details of the work and worries about ‘designer babies’.

The interest flurry

I found three articles addressing the research and all three concur that despite some of the early reporting, this is not the beginning of a ‘designer baby’ generation.

First up was Nick Thieme in a July 28, 2017 article for Slate,

MIT Technology Review reported Thursday that a team of researchers from Portland, Oregon were the first team of U.S.-based scientists to successfully create a genetically modified human embryo. The researchers, led by Shoukhrat Mitalipov of Oregon Health and Science University, changed the DNA of—in MIT Technology Review’s words—“many tens” of genetically-diseased embryos by injecting the host egg with CRISPR, a DNA-based gene editing tool first discovered in bacteria, at the time of fertilization. CRISPR-Cas9, as the full editing system is called, allows scientists to change genes accurately and efficiently. As has happened with research elsewhere, the CRISPR-edited embryos weren’t implanted—they were kept sustained for only a couple of days.

In addition to being the first American team to complete this feat, the researchers also improved upon the work of the three Chinese research teams that beat them to editing embryos with CRISPR: Mitalipov’s team increased the proportion of embryonic cells that received the intended genetic changes, addressing an issue called “mosaicism,” which is when an embryo is comprised of cells with different genetic makeups. Increasing that proportion is essential to CRISPR work in eliminating inherited diseases, to ensure that the CRISPR therapy has the intended result. The Oregon team also reduced the number of genetic errors introduced by CRISPR, reducing the likelihood that a patient would develop cancer elsewhere in the body.

Separate from the scientific advancements, it’s a big deal that this work happened in a country with such intense politicization of embryo research. …

But there are a great number of obstacles between the current research and the future of genetically editing all children to be 12-foot-tall Einsteins.

Ed Yong in an Aug. 2, 2017 article for The Atlantic offered a comprehensive overview of the research and its implications (unusually for Yong, there seems to be mildly condescending note but it’s worth ignoring for the wealth of information in the article; Note: Links have been removed),

… the full details of the experiment, which are released today, show that the study is scientifically important but much less of a social inflection point than has been suggested. “This has been widely reported as the dawn of the era of the designer baby, making it probably the fifth or sixth time people have reported that dawn,” says Alta Charo, an expert on law and bioethics at the University of Wisconsin-Madison. “And it’s not.”

Given the persistent confusion around CRISPR and its implications, I’ve laid out exactly what the team did, and what it means.

Who did the experiments?

Shoukhrat Mitalipov is a Kazakhstani-born cell biologist with a history of breakthroughs—and controversy—in the stem cell field. He was the scientist to clone monkeys. He was the first to create human embryos by cloning adult cells—a move that could provide patients with an easy supply of personalized stem cells. He also pioneered a technique for creating embryos with genetic material from three biological parents, as a way of preventing a group of debilitating inherited diseases.

Although MIT Tech Review name-checked Mitalipov alone, the paper splits credit for the research between five collaborating teams—four based in the United States, and one in South Korea.

What did they actually do?

The project effectively began with an elevator conversation between Mitalipov and his colleague Sanjiv Kaul. Mitalipov explained that he wanted to use CRISPR to correct a disease-causing gene in human embryos, and was trying to figure out which disease to focus on. Kaul, a cardiologist, told him about hypertrophic cardiomyopathy (HCM)—an inherited heart disease that’s commonly caused by mutations in a gene called MYBPC3. HCM is surprisingly common, affecting 1 in 500 adults. Many of them lead normal lives, but in some, the walls of their hearts can thicken and suddenly fail. For that reason, HCM is the commonest cause of sudden death in athletes. “There really is no treatment,” says Kaul. “A number of drugs are being evaluated but they are all experimental,” and they merely treat the symptoms. The team wanted to prevent HCM entirely by removing the underlying mutation.

They collected sperm from a man with HCM and used CRISPR to change his mutant gene into its normal healthy version, while simultaneously using the sperm to fertilize eggs that had been donated by female volunteers. In this way, they created embryos that were completely free of the mutation. The procedure was effective, and avoided some of the critical problems that have plagued past attempts to use CRISPR in human embryos.

Wait, other human embryos have been edited before?

There have been three attempts in China. The first two—in 2015 and 2016—used non-viable embryos that could never have resulted in a live birth. The third—announced this March—was the first to use viable embryos that could theoretically have been implanted in a womb. All of these studies showed that CRISPR gene-editing, for all its hype, is still in its infancy.

The editing was imprecise. CRISPR is heralded for its precision, allowing scientists to edit particular genes of choice. But in practice, some of the Chinese researchers found worrying levels of off-target mutations, where CRISPR mistakenly cut other parts of the genome.

The editing was inefficient. The first Chinese team only managed to successfully edit a disease gene in 4 out of 86 embryos, and the second team fared even worse.

The editing was incomplete. Even in the successful cases, each embryo had a mix of modified and unmodified cells. This pattern, known as mosaicism, poses serious safety problems if gene-editing were ever to be used in practice. Doctors could end up implanting women with embryos that they thought were free of a disease-causing mutation, but were only partially free. The resulting person would still have many tissues and organs that carry those mutations, and might go on to develop symptoms.

What did the American team do differently?

The Chinese teams all used CRISPR to edit embryos at early stages of their development. By contrast, the Oregon researchers delivered the CRISPR components at the earliest possible point—minutes before fertilization. That neatly avoids the problem of mosaicism by ensuring that an embryo is edited from the very moment it is created. The team did this with 54 embryos and successfully edited the mutant MYBPC3 gene in 72 percent of them. In the other 28 percent, the editing didn’t work—a high failure rate, but far lower than in previous attempts. Better still, the team found no evidence of off-target mutations.

This is a big deal. Many scientists assumed that they’d have to do something more convoluted to avoid mosaicism. They’d have to collect a patient’s cells, which they’d revert into stem cells, which they’d use to make sperm or eggs, which they’d edit using CRISPR. “That’s a lot of extra steps, with more risks,” says Alta Charo. “If it’s possible to edit the embryo itself, that’s a real advance.” Perhaps for that reason, this is the first study to edit human embryos that was published in a top-tier scientific journal—Nature, which rejected some of the earlier Chinese papers.

Is this kind of research even legal?

Yes. In Western Europe, 15 countries out of 22 ban any attempts to change the human germ line—a term referring to sperm, eggs, and other cells that can transmit genetic information to future generations. No such stance exists in the United States but Congress has banned the Food and Drug Administration from considering research applications that make such modifications. Separately, federal agencies like the National Institutes of Health are banned from funding research that ultimately destroys human embryos. But the Oregon team used non-federal money from their institutions, and donations from several small non-profits. No taxpayer money went into their work. [emphasis mine]

Why would you want to edit embryos at all?

Partly to learn more about ourselves. By using CRISPR to manipulate the genes of embryos, scientists can learn more about the earliest stages of human development, and about problems like infertility and miscarriages. That’s why biologist Kathy Niakan from the Crick Institute in London recently secured a license from a British regulator to use CRISPR on human embryos.

Isn’t this a slippery slope toward making designer babies?

In terms of avoiding genetic diseases, it’s not conceptually different from PGD, which is already widely used. The bigger worry is that gene-editing could be used to make people stronger, smarter, or taller, paving the way for a new eugenics, and widening the already substantial gaps between the wealthy and poor. But many geneticists believe that such a future is fundamentally unlikely because complex traits like height and intelligence are the work of hundreds or thousands of genes, each of which have a tiny effect. The prospect of editing them all is implausible. And since genes are so thoroughly interconnected, it may be impossible to edit one particular trait without also affecting many others.

“There’s the worry that this could be used for enhancement, so society has to draw a line,” says Mitalipov. “But this is pretty complex technology and it wouldn’t be hard to regulate it.”

Does this discovery have any social importance at all?

“It’s not so much about designer babies as it is about geographical location,” says Charo. “It’s happening in the United States, and everything here around embryo research has high sensitivity.” She and others worry that the early report about the study, before the actual details were available for scrutiny, could lead to unnecessary panic. “Panic reactions often lead to panic-driven policy … which is usually bad policy,” wrote Greely [bioethicist Hank Greely].

As I understand it, despite the change in stance, there is no federal funding available for the research performed by Mitalipov and his team.

Finally, University College London (UCL) scientists Joyce Harper and Helen O’Neill wrote about CRISPR, the Oregon team’s work, and the possibilities in an Aug. 3, 2017 essay for The Conversation (Note: Links have been removed),

The genome editing tool used, CRISPR-Cas9, has transformed the field of biology in the short time since its discovery in that it not only promises, but delivers. CRISPR has surpassed all previous efforts to engineer cells and alter genomes at a fraction of the time and cost.

The technology, which works like molecular scissors to cut and paste DNA, is a natural defence system that bacteria use to fend off harmful infections. This system has the ability to recognise invading virus DNA, cut it and integrate this cut sequence into its own genome – allowing the bacterium to render itself immune to future infections of viruses with similar DNA. It is this ability to recognise and cut DNA that has allowed scientists to use it to target and edit specific DNA regions.

When this technology is applied to “germ cells” – the sperm and eggs – or embryos, it changes the germline. That means that any alterations made would be permanent and passed down to future generations. This makes it more ethically complex, but there are strict regulations around human germline genome editing, which is predominantly illegal. The UK received a licence in 2016 to carry out CRISPR on human embryos for research into early development. But edited embryos are not allowed to be inserted into the uterus and develop into a fetus in any country.

Germline genome editing came into the global spotlight when Chinese scientists announced in 2015 that they had used CRISPR to edit non-viable human embryos – cells that could never result in a live birth. They did this to modify the gene responsible for the blood disorder β-thalassaemia. While it was met with some success, it received a lot of criticism because of the premature use of this technology in human embryos. The results showed a high number of potentially dangerous, off-target mutations created in the procedure.

Impressive results

The new study, published in Nature, is different because it deals with viable human embryos and shows that the genome editing can be carried out safely – without creating harmful mutations. The team used CRISPR to correct a mutation in the gene MYBPC3, which accounts for approximately 40% of the myocardial disease hypertrophic cardiomyopathy. This is a dominant disease, so an affected individual only needs one abnormal copy of the gene to be affected.

The researchers used sperm from a patient carrying one copy of the MYBPC3 mutation to create 54 embryos. They edited them using CRISPR-Cas9 to correct the mutation. Without genome editing, approximately 50% of the embryos would carry the patients’ normal gene and 50% would carry his abnormal gene.

After genome editing, the aim would be for 100% of embryos to be normal. In the first round of the experiments, they found that 66.7% of embryos – 36 out of 54 – were normal after being injected with CRIPSR. Of the remaining 18 embryos, five had remained unchanged, suggesting editing had not worked. In 13 embryos, only a portion of cells had been edited.

The level of efficiency is affected by the type of CRISPR machinery used and, critically, the timing in which it is put into the embryo. The researchers therefore also tried injecting the sperm and the CRISPR-Cas9 complex into the egg at the same time, which resulted in more promising results. This was done for 75 mature donated human eggs using a common IVF technique called intracytoplasmic sperm injection. This time, impressively, 72.4% of embryos were normal as a result. The approach also lowered the number of embryos containing a mixture of edited and unedited cells (these embryos are called mosaics).

Finally, the team injected a further 22 embryos which were grown into blastocyst – a later stage of embryo development. These were sequenced and the researchers found that the editing had indeed worked. Importantly, they could show that the level of off-target mutations was low.

A brave new world?

So does this mean we finally have a cure for debilitating, heritable diseases? It’s important to remember that the study did not achieve a 100% success rate. Even the researchers themselves stress that further research is needed in order to fully understand the potential and limitations of the technique.

In our view, it is unlikely that genome editing would be used to treat the majority of inherited conditions anytime soon. We still can’t be sure how a child with a genetically altered genome will develop over a lifetime, so it seems unlikely that couples carrying a genetic disease would embark on gene editing rather than undergoing already available tests – such as preimplantation genetic diagnosis or prenatal diagnosis – where the embryos or fetus are tested for genetic faults.

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As might be expected there is now a call for public discussion about the ethics about this kind of work. See Part 3.

For anyone who started in the middle of this series, here’s Part 1 featuring an introduction to the technology and some of the issues.

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

There’s been a minor flurry of interest in CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats; also known as CRISPR-CAS9), a gene-editing technique, since a team in Oregon announced a paper describing their work editing the germline. Since I’ve been following the CRISPR-CAS9 story for a while this seems like a good juncture for a more in-depth look at the topic. In this first part I’m including an introduction to CRISPR, some information about the latest US work, and some previous writing about ethics issues raised when Chinese scientists first announced their work editing germlines in 2015 and during the patent dispute between the University of California at Berkeley and Harvard University’s Broad Institute.

Introduction to CRISPR

I’ve been searching for a good description of CRISPR and this helped to clear up some questions for me (Thank you to MIT Review),

For anyone who’s been reading about science for a while, this upbeat approach to explaining how a particular technology will solve all sorts of problems will seem quite familiar. It’s not the most hyperbolic piece I’ve seen but it barely mentions any problems associated with research (for some of the problems see: ‘The interest flurry’ later in part 2).

Oregon team

Steve Connor’s July 26, 2017 article for the MIT (Massachusetts Institute of Technology) Technology Review breaks the news (Note: Links have been removed),

The first known attempt at creating genetically modified human embryos in the United States has been carried out by a team of researchers in Portland, Oregon, MIT Technology Review has learned.

The effort, led by Shoukhrat Mitalipov of Oregon Health and Science University, involved changing the DNA of a large number of one-cell embryos with the gene-editing technique CRISPR, according to people familiar with the scientific results.

Until now, American scientists have watched with a combination of awe, envy, and some alarm as scientists elsewhere were first to explore the controversial practice. To date, three previous reports of editing human embryos were all published by scientists in China.

Now Mitalipov is believed to have broken new ground both in the number of embryos experimented upon and by demonstrating that it is possible to safely and efficiently correct defective genes that cause inherited diseases.

Although none of the embryos were allowed to develop for more than a few days—and there was never any intention of implanting them into a womb—the experiments are a milestone on what may prove to be an inevitable journey toward the birth of the first genetically modified humans.

In altering the DNA code of human embryos, the objective of scientists is to show that they can eradicate or correct genes that cause inherited disease, like the blood condition beta-thalassemia. The process is termed “germline engineering” because any genetically modified child would then pass the changes on to subsequent generations via their own germ cells—the egg and sperm.

Some critics say germline experiments could open the floodgates to a brave new world of “designer babies” engineered with genetic enhancements—a prospect bitterly opposed by a range of religious organizations, civil society groups, and biotech companies.

The U.S. intelligence community last year called CRISPR a potential “weapon of mass destruction.”

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

Correction of a pathogenic gene mutation in human embryos by Hong Ma, Nuria Marti-Gutierrez, Sang-Wook Park, Jun Wu, Yeonmi Lee, Keiichiro Suzuki, Amy Koski, Dongmei Ji, Tomonari Hayama, Riffat Ahmed, Hayley Darby, Crystal Van Dyken, Ying Li, Eunju Kang, A.-Reum Park, Daesik Kim, Sang-Tae Kim, Jianhui Gong, Ying Gu, Xun Xu, David Battaglia, Sacha A. Krieg, David M. Lee, Diana H. Wu, Don P. Wolf, Stephen B. Heitner, Juan Carlos Izpisua Belmonte, Paula Amato, Jin-Soo Kim, Sanjiv Kaul, & Shoukhrat Mitalipov. Nature (2017) doi:10.1038/nature23305 Published online 02 August 2017

This paper appears to be open access.

CRISPR Issues: ethics and patents

In my May 14, 2015 posting I mentioned a ‘moratorium’ on germline research, the Chinese research paper, and the stance taken by the US National Institutes of Health (NIH),

The CRISPR technology has reignited a discussion about ethical and moral issues of human genetic engineering some of which is reviewed in an April 7, 2015 posting about a moratorium by Sheila Jasanoff, J. Benjamin Hurlbut and Krishanu Saha for the Guardian science blogs (Note: A link has been removed),

On April 3, 2015, a group of prominent biologists and ethicists writing in Science called for a moratorium on germline gene engineering; modifications to the human genome that will be passed on to future generations. The moratorium would apply to a technology called CRISPR/Cas9, which enables the removal of undesirable genes, insertion of desirable ones, and the broad recoding of nearly any DNA sequence.

Such modifications could affect every cell in an adult human being, including germ cells, and therefore be passed down through the generations. Many organisms across the range of biological complexity have already been edited in this way to generate designer bacteria, plants and primates. There is little reason to believe the same could not be done with human eggs, sperm and embryos. Now that the technology to engineer human germlines is here, the advocates for a moratorium declared, it is time to chart a prudent path forward. They recommend four actions: a hold on clinical applications; creation of expert forums; transparent research; and a globally representative group to recommend policy approaches.

The authors go on to review precedents and reasons for the moratorium while suggesting we need better ways for citizens to engage with and debate these issues,

An effective moratorium must be grounded in the principle that the power to modify the human genome demands serious engagement not only from scientists and ethicists but from all citizens. We need a more complex architecture for public deliberation, built on the recognition that we, as citizens, have a duty to participate in shaping our biotechnological futures, just as governments have a duty to empower us to participate in that process. Decisions such as whether or not to edit human genes should not be left to elite and invisible experts, whether in universities, ad hoc commissions, or parliamentary advisory committees. Nor should public deliberation be temporally limited by the span of a moratorium or narrowed to topics that experts deem reasonable to debate.

I recommend reading the post in its entirety as there are nuances that are best appreciated in the entirety of the piece.

Shortly after this essay was published, Chinese scientists announced they had genetically modified (nonviable) human embryos. From an April 22, 2015 article by David Cyranoski and Sara Reardon in Nature where the research and some of the ethical issues discussed,

In a world first, Chinese scientists have reported editing the genomes of human embryos. The results are published1 in the online journal Protein & Cell and confirm widespread rumours that such experiments had been conducted — rumours that sparked a high-profile debate last month2, 3 about the ethical implications of such work.

In the paper, researchers led by Junjiu Huang, a gene-function researcher at Sun Yat-sen University in Guangzhou, tried to head off such concerns by using ‘non-viable’ embryos, which cannot result in a live birth, that were obtained from local fertility clinics. The team attempted to modify the gene responsible for β-thalassaemia, a potentially fatal blood disorder, using a gene-editing technique known as CRISPR/Cas9. The researchers say that their results reveal serious obstacles to using the method in medical applications.

“I believe this is the first report of CRISPR/Cas9 applied to human pre-implantation embryos and as such the study is a landmark, as well as a cautionary tale,” says George Daley, a stem-cell biologist at Harvard Medical School in Boston, Massachusetts. “Their study should be a stern warning to any practitioner who thinks the technology is ready for testing to eradicate disease genes.”

….

Huang says that the paper was rejected by Nature and Science, in part because of ethical objections; both journals declined to comment on the claim. (Nature’s news team is editorially independent of its research editorial team.)

He adds that critics of the paper have noted that the low efficiencies and high number of off-target mutations could be specific to the abnormal embryos used in the study. Huang acknowledges the critique, but because there are no examples of gene editing in normal embryos he says that there is no way to know if the technique operates differently in them.

Still, he maintains that the embryos allow for a more meaningful model — and one closer to a normal human embryo — than an animal model or one using adult human cells. “We wanted to show our data to the world so people know what really happened with this model, rather than just talking about what would happen without data,” he says.

This, too, is a good and thoughtful read.

There was an official response in the US to the publication of this research, from an April 29, 2015 post by David Bruggeman on his Pasco Phronesis blog (Note: Links have been removed),

In light of Chinese researchers reporting their efforts to edit the genes of ‘non-viable’ human embryos, the National Institutes of Health (NIH) Director Francis Collins issued a statement (H/T Carl Zimmer).

“NIH will not fund any use of gene-editing technologies in human embryos. The concept of altering the human germline in embryos for clinical purposes has been debated over many years from many different perspectives, and has been viewed almost universally as a line that should not be crossed. Advances in technology have given us an elegant new way of carrying out genome editing, but the strong arguments against engaging in this activity remain. These include the serious and unquantifiable safety issues, ethical issues presented by altering the germline in a way that affects the next generation without their consent, and a current lack of compelling medical applications justifying the use of CRISPR/Cas9 in embryos.” …

The US has modified its stance according to a February 14, 2017 article by Jocelyn Kaiser for Science Magazine (Note: Links have been removed),

Editing the DNA of a human embryo to prevent a disease in a baby could be ethically allowable one day—but only in rare circumstances and with safeguards in place, says a widely anticipated report released today.

The report from an international committee convened by the U.S. National Academy of Sciences (NAS) and the National Academy of Medicine in Washington, D.C., concludes that such a clinical trial “might be permitted, but only following much more research” on risks and benefits, and “only for compelling reasons and under strict oversight.” Those situations could be limited to couples who both have a serious genetic disease and for whom embryo editing is “really the last reasonable option” if they want to have a healthy biological child, says committee co-chair Alta Charo, a bioethicist at the University of Wisconsin in Madison.

Some researchers are pleased with the report, saying it is consistent with previous conclusions that safely altering the DNA of human eggs, sperm, or early embryos—known as germline editing—to create a baby could be possible eventually. “They have closed the door to the vast majority of germline applications and left it open for a very small, well-defined subset. That’s not unreasonable in my opinion,” says genome researcher Eric Lander of the Broad Institute in Cambridge, Massachusetts. Lander was among the organizers of an international summit at NAS in December 2015 who called for more discussion before proceeding with embryo editing.

But others see the report as lowering the bar for such experiments because it does not explicitly say they should be prohibited for now. “It changes the tone to an affirmative position in the absence of the broad public debate this report calls for,” says Edward Lanphier, chairman of the DNA editing company Sangamo Therapeutics in Richmond, California. Two years ago, he co-authored a Nature commentary calling for a moratorium on clinical embryo editing.

One advocacy group opposed to embryo editing goes further. “We’re very disappointed with the report. It’s really a pretty dramatic shift from the existing and widespread agreement globally that human germline editing should be prohibited,” says Marcy Darnovsky, executive director of the Center for Genetics and Society in Berkeley, California.

Interestingly, this change of stance occurred just prior to a CRISPR patent decision (from my March 15, 2017 posting),

I have written about the CRISPR patent tussle (Harvard & MIT’s [Massachusetts Institute of Technology] Broad Institute vs the University of California at Berkeley) previously in a Jan. 6, 2015 posting and in a more detailed May 14, 2015 posting. I also mentioned (in a Jan. 17, 2017 posting) CRISPR and its patent issues in the context of a posting about a Slate.com series on Frankenstein and the novel’s applicability to our own time. This patent fight is being bitterly fought as fortunes are at stake.

It seems a decision has been made regarding the CRISPR patent claims. From a Feb. 17, 2017 article by Charmaine Distor for The Science Times,

After an intense court battle, the US Patent and Trademark Office (USPTO) released its ruling on February 15 [2017]. The rights for the CRISPR-Cas9 gene editing technology was handed over to the Broad Institute of Harvard University and the Massachusetts Institute of Technology (MIT).

According to an article in Nature, the said court battle was between the Broad Institute and the University of California. The two institutions are fighting over the intellectual property right for the CRISPR patent. The case between the two started when the patent was first awarded to the Broad Institute despite having the University of California apply first for the CRISPR patent.

Heidi Ledford’s Feb. 17, 2017 article for Nature provides more insight into the situation (Note: Links have been removed),

It [USPTO] ruled that the Broad Institute of Harvard and MIT in Cambridge could keep its patents on using CRISPR–Cas9 in eukaryotic cells. That was a blow to the University of California in Berkeley, which had filed its own patents and had hoped to have the Broad’s thrown out.

The fight goes back to 2012, when Jennifer Doudna at Berkeley, Emmanuelle Charpentier, then at the University of Vienna, and their colleagues outlined how CRISPR–Cas9 could be used to precisely cut isolated DNA1. In 2013, Feng Zhang at the Broad and his colleagues — and other teams — showed2 how it could be adapted to edit DNA in eukaryotic cells such as plants, livestock and humans.

Berkeley filed for a patent earlier, but the USPTO granted the Broad’s patents first — and this week upheld them. There are high stakes involved in the ruling. The holder of key patents could make millions of dollars from CRISPR–Cas9’s applications in industry: already, the technique has sped up genetic research, and scientists are using it to develop disease-resistant livestock and treatments for human diseases.

….

I also noted this eyebrow-lifting statistic,  “As for Ledford’s 3rd point, there are an estimated 763 patent families (groups of related patents) claiming CAS9 leading to the distinct possibility that the Broad Institute will be fighting many patent claims in the future.)

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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

Nanoparticle behaviour in the environment unpredictable

These Swiss researchers took on a fairly massive project according to an April 19, 2017 news item on ScienceDaily,

The nanotech industry is booming. Every year, several thousands of tonnes of man-made nanoparticles are produced worldwide; sooner or later, a certain part of them will end up in bodies of water or soil. But even experts find it difficult to say exactly what happens to them there. It is a complex question, not only because there are many different types of man-made (engineered) nanoparticles, but also because the particles behave differently in the environment depending on the prevailing conditions.

Researchers led by Martin Scheringer, Senior Scientist at the Department of Chemistry and Applied Biosciences, wanted to bring some clarity to this issue. They reviewed 270 scientific studies, and the nearly 1,000 laboratory experiments described in them, looking for patterns in the behaviour of engineered nanoparticles. The goal was to make universal predictions about the behaviour of the particles.

An April 19, 2017ETH Zurich press release by Fabio Bergamin (also on EurekAlert), which originated the news item, elaborates,

Particles attach themselves to everything

However, the researchers found a very mixed picture when they looked at the data. “The situation is more complex than many scientists would previously have predicted,” says Scheringer. “We need to recognise that we can’t draw a uniform picture with the data available to us today.”

Nicole Sani-Kast, a doctoral student in Scheringer’s group and first author of the analysis published in the journal PNAS [Proceedings of the National Academy of Sciences], adds: “Engineered nanoparticles behave very dynamically and are highly reactive. They attach themselves to everything they find: to other nanoparticles in order to form agglomerates, or to other molecules present in the environment.”

Network analysis

To what exactly the particles react, and how quickly, depends on various factors such as the acidity of the water or soil, the concentration of the existing minerals and salts, and above all, the composition of the organic substances dissolved in the water or present in the soil. The fact that the engineered nanoparticles often have a surface coating makes things even more complicated. Depending on the environmental conditions, the particles retain or lose their coating, which in turn influences their reaction behaviour.

To evaluate the results available in the literature, Sani-Kast used a network analysis for the first time in this research field. It is a technique familiar in social research for measuring networks of social relations, and allowed her to show that the data available on engineered nanoparticles is inconsistent, insufficiently diverse and poorly structured.

More method for machine learning

“If more structured, consistent and sufficiently diverse data were available, it may be possible to discover universal patterns using machine learning methods,” says Scheringer, “but we’re not there yet.” Enough structured experimental data must first be available.

“In order for the scientific community to carry out such experiments in a systematic and standardised manner, some kind of coordination is necessary,” adds Sani-Kast, but she is aware that such work is difficult to coordinate. Scientists are generally well known for preferring to explore new methods and conditions rather than routinely performing standardized experiments.

[additional material]

Distinguishing man-made and natural nanoparticles

In addition to the lack of systematic research, there is also a second tangible problem in researching the behaviour of engineered nanoparticles: many engineered nanoparticles consist of chemical compounds that occur naturally in the soil. So far it has been difficult to measure the engineered particles in the environment since it is hard to distinguish them from naturally occurring particles with the same chemical composition.

However, researchers at ETH Zurich’s Department of Chemistry and Applied Biosciences, under the direction of ETH Professor Detlef Günther, have recently established an effective method that makes such a distinction possible in routine investigations. They used a state-of-the-art and highly sensitive mass spectrometry technique (called spICP-TOF mass spectrometry) to determine which chemical elements make up individual nanoparticles in a sample.

In collaboration with scientists from the University of Vienna, the ETH researchers applied the method to soil samples with natural cerium-containing particles, into which they mixed engineered cerium dioxide nanoparticles. Using machine learning methods, which were ideally suited to this particular issue, the researchers were able to identify differences in the chemical fingerprints of the two particle classes. “While artificially produced nanoparticles often consist of a single compound, natural nanoparticles usually still contain a number of additional chemical elements,” explains Alexander Gundlach-Graham, a postdoc in Günther’s group.

The new measuring method is very sensitive: the scientists were able to measure engineered particles in samples with up to one hundred times more natural particles.

The researchers have produced a visualization of their network analysis,

The researchers evaluated the experimental data published in the scientific literature using a network analysis. This analysis reveals which types of nanoparticles (blue) have been studied under which environmental conditions (red). (Visualisations: Thomas Kast)

Here are links and citation for two papers associated with this research,

A network perspective reveals decreasing material diversity in studies on nanoparticle interactions with dissolved organic matter by Nicole Sani-Kast, Jérôme Labille, Patrick Ollivier, Danielle Slomberg, Konrad Hungerbühler, and Martin Scheringer. PNAS 2017, 114: E1756-E1765, DOI: 10.1073/pnas.1608106114

Single-particle multi-element fingerprinting (spMEF) using inductively-coupled plasma time-of-flight mass spectrometry (ICP-TOFMS) to identify engineered nanoparticles against the elevated natural background in soils by Antonia Praetorius, Alexander Gundlach-Graham, Eli Goldberg, Willi Fabienke, Jana Navratilova, Andreas Gondikas, Ralf Kaegi, Detlef Günther, Thilo Hofmann, and Frank von der Kammer. Environonmental Science: Nano 2017, 4: 307-314, DOI: 10.1039/c6en00455e

Both papers are behind a paywall.

CRISPR patent decision: Harvard’s and MIT’s Broad Institute victorious—for now

I have written about the CRISPR patent tussle (Harvard & MIT’s [Massachusetts Institute of Technology] Broad Institute vs the University of California at Berkeley) previously in a Jan. 6, 2015 posting and in a more detailed May 14, 2015 posting. I also mentioned (in a Jan. 17, 2017 posting) CRISPR and its patent issues in the context of a posting about a Slate.com series on Frankenstein and the novel’s applicability to our own time. This patent fight is being bitterly fought as fortunes are at stake.

It seems a decision has been made regarding the CRISPR patent claims. From a Feb. 17, 2017 article by Charmaine Distor for The Science Times,

After an intense court battle, the US Patent and Trademark Office (USPTO) released its ruling on February 15 [2017]. The rights for the CRISPR-Cas9 gene editing technology was handed over to the Broad Institute of Harvard University and the Massachusetts Institute of Technology (MIT).

According to an article in Nature, the said court battle was between the Broad Institute and the University of California. The two institutions are fighting over the intellectual property right for the CRISPR patent. The case between the two started when the patent was first awarded to the Broad Institute despite having the University of California apply first for the CRISPR patent.

Heidi Ledford’s Feb. 17, 2017 article for Nature provides more insight into the situation (Note: Links have been removed),

It [USPTO] ruled that the Broad Institute of Harvard and MIT in Cambridge could keep its patents on using CRISPR–Cas9 in eukaryotic cells. That was a blow to the University of California in Berkeley, which had filed its own patents and had hoped to have the Broad’s thrown out.

The fight goes back to 2012, when Jennifer Doudna at Berkeley, Emmanuelle Charpentier, then at the University of Vienna, and their colleagues outlined how CRISPR–Cas9 could be used to precisely cut isolated DNA1. In 2013, Feng Zhang at the Broad and his colleagues — and other teams — showed2 how it could be adapted to edit DNA in eukaryotic cells such as plants, livestock and humans.

Berkeley filed for a patent earlier, but the USPTO granted the Broad’s patents first — and this week upheld them. There are high stakes involved in the ruling. The holder of key patents could make millions of dollars from CRISPR–Cas9’s applications in industry: already, the technique has sped up genetic research, and scientists are using it to develop disease-resistant livestock and treatments for human diseases.

But the fight for patent rights to CRISPR technology is by no means over. Here are four reasons why.

1. Berkeley can appeal the ruling

2. European patents are still up for grabs

3. Other parties are also claiming patent rights on CRISPR–Cas9

4. CRISPR technology is moving beyond what the patents cover

As for Ledford’s 3rd point, there are an estimated 763 patent families (groups of related patents) claiming CAS9 leading to the distinct possibility that the Broad Institute will be fighting many patent claims in the future.

Once you’ve read Distor’s and Ledford’s articles, you may want to check out Adam Rogers’ and Eric Niiler’s Feb. 16, 2017 CRISPR patent article for Wired,

The fight over who owns the most promising technique for editing genes—cutting and pasting the stuff of life to cure disease and advance scientific knowledge—has been a rough one. A team on the West Coast, at UC Berkeley, filed patents on the method, Crispr-Cas9; a team on the East Coast, based at MIT and the Broad Institute, filed their own patents in 2014 after Berkeley’s, but got them granted first. The Berkeley group contended that this constituted “interference,” and that Berkeley deserved the patent.

At stake: millions, maybe billions of dollars in biotech money and licensing fees, the future of medicine, the future of bioscience. Not nothing. Who will benefit depends on who owns the patents.

On Wednesday [Feb. 15, 2017], the US Patent Trial and Appeal Board kind of, sort of, almost began to answer that question. Berkeley will get the patent for using the system called Crispr-Cas9 in any living cell, from bacteria to blue whales. Broad/MIT gets the patent in eukaryotic cells, which is to say, plants and animals.

It’s … confusing. “The patent that the Broad received is for the use of Crispr gene-editing technology in eukaryotic cells. The patent for the University of California is for all cells,” says Jennifer Doudna, the UC geneticist and co-founder of Caribou Biosciences who co-invented Crispr, on a conference call. Her metaphor: “They have a patent on green tennis balls; we have a patent for all tennis balls.”

Observers didn’t quite buy that topspin. If Caribou is playing tennis, it’s looking like Broad/MIT is Serena Williams.

“UC does not necessarily lose everything, but they’re no doubt spinning the story,” says Robert Cook-Deegan, an expert in genetic policy at Arizona State University’s School for the Future of Innovation in Society. “UC’s claims to eukaryotic uses of Crispr-Cas9 will not be granted in the form they sought. That’s a big deal, and UC was the big loser.”

UC officials said Wednesday [Feb. 15, 2017] that they are studying the 51-page decision and considering whether to appeal. That leaves members of the biotechnology sector wondering who they will have to pay to use Crispr as part of a business—and scientists hoping the outcome won’t somehow keep them from continuing their research.

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Happy reading!