Author Archives: Maryse de la Giroday

Masdar Institute and rainmaking

Water security, of course, is a key issue and of particular concern in many parts of the world including the Middle East. (In the Pacific Northwest, an area described as a temperate rain forest, there tends to be less awareness but even we are sometimes forced to ration water.) According to a July 5, 2017 posting by Bhok Thompson (on the Green Prophet website) scientists at the Masdar Institute of Science and Technology (in Abu Dhabi, United Arab Emirates [UA]E) have applied for a patent on a new technique for rainmaking,

Umbrella sales in the UAE may soon see a surge in pricing. Researchers at the Masdar Institute have filed for a provisional patent with the United States Patent and Trademark Office for their discovery – and innovative cloud seeding material that moves them closer to their goal of producing rain on demand. It appears to be a more practical approach than building artificial mountains.

Dr. Linda Zou is leading the project. A professor of chemical and environmental engineering, she is one of the first scientists to explore nanotechnology to enhance a cloud seeding material’s ability to produce rain. By filing a patent, the team is paving a way to commercialize their discovery, and aligning with Masdar Institute’s aim to position the UAE as a world leader in science and tech, specifically in the realm of environmental sustainability.

A January 31, 2017 posting by Erica Solomon for the Masdar Institute reveals more about the project,

The Masdar Institute research team that was one of the inaugural recipients of the US$ 5 million grant from the UAE Research Program for Rain Enhancement Science last year has made significant progress in their work as evidenced by the filing a provisional patent with the United States Patent and Trademark Office (USPTO).

By filing a patent on their innovative cloud seeding material, the research team is bringing the material in the pathway for commercialization, thereby supporting Masdar Institute’s goal of bolstering the United Arab Emirates’ local intellectual property, which is a key measure of the country’s innovation drive. It also signifies a milestone towards achieving greater water security in the UAE, as rainfall enhancement via cloud seeding can potentially increase rainfall between 10% to 30%, helping to refresh groundwater reserves, boost agricultural production, and reduce the country’s heavy reliance on freshwater produced by energy-intensive seawater desalination.

Masdar Institute Professor of Chemical and Environmental Engineering, Dr. Linda Zou, is the principal investigator of this research project, and one of the first scientists in the world to explore the use of nanotechnology to enhance a cloud seeding material’s ability to produce rain.

“Using nanotechnology to accelerate water droplet formation on a typical cloud seeding material has never been researched before. It is a new approach that could revolutionize the development of cloud seeding materials and make them significantly more efficient and effective,” Dr. Zou remarked.

Conventional cloud seeding materials are small particles such as pure salt crystals, dry ice and silver iodide. These tiny particles, which are a few microns (one-thousandth of a millimeter) in size, act as the core around which water condenses in the clouds, stimulating water droplet growth. Once the air in the cloud reaches a certain level of saturation, it can no longer hold in that moisture, and rain falls. Cloud seeding essentially mimics what naturally occurs in clouds, but enhances the process by adding particles that can stimulate and accelerate the condensation process.

Dr. Zou and her collaborators, Dr. Mustapha Jouiad, Principal Research Scientist in Mechanical and Materials Engineering Department, postdoctoral researcher Dr. Nabil El Hadri and PhD student Haoran Liang, explored ways to improve the process of condensation on a pure salt crystal by layering it with a thin coating of titanium dioxide.

The extremely thin coating measures around 50 nanometers, which is more than one thousand times thinner than a human hair. Despite the coating’s miniscule size, the titanium dioxide’s effect on the salt’s condensation efficiency is significant. Titanium dioxide is a hydrophilic photocatalyst, which means that when in contact with water vapor in the cloud, it helps to initiate and sustain the water vapor adsorption and condensation on the nanoparticle’s surface. This important property of the cloud seeding material speeds up the formation of large water droplets for rainfall.

Dr. Zou’s team found that the titanium dioxide coating improved the salt’s ability to adsorb and condense water vapor over 100 times compared to a pure salt crystal. Such an increase in condensation efficiency could improve a cloud’s ability to produce more precipitation, making rain enhancement operations more efficient and effective. The research will now move to the next stage of simulated cloud and field testing in the future.

Dr. Zou’s research grant covers two more years of research. During this time, her team will continue to study different design concepts and structures for cloud seeding materials inspired by nanotechnology.

To give you a sense of the urgent need for these technologies, here’s the title from my Aug. 24, 2015 posting, The Gaza is running out of water by 2016 if the United Nations predictions are correct. I’ve not come across any updates on the situation in the Gaza Strip but both Israel and Palestine have recently signed a deal concerning water. Dalia Hatuqa’s August 2017 feature on the water deal for Al Jazeera is critical primarily of Israel (as might be expected) but there are one or two subtle criticisms of Palestine too,

Critics have also warned that the plan does not address Israeli restrictions on Palestinian access to water and the development of infrastructure needed to address the water crisis in the occupied West Bank.

Palestinians in the West Bank consume only 70 litres of water per capita per day, well below what the World Health Organization recommends as a minimum (100).

In the most vulnerable communities in Area C – those not connected to the water network – that number further drops to 20, according to EWASH, a coalition of Palestinian and international organisations working on water and sanitation in the Palestinian territories.

The recent bilateral agreement, which does not increase the Palestinians’ quota of water in the Jordan River, makes an untenable situation permanent and guarantees Israel a lion’s share of its water, thus reinforcing the status quo, Buttu [Diana Buttu, a former adviser to the Palestinian negotiating team] said.

“They have moved away from the idea that water is a shared resource and instead adopted the approach that Israel controls and allocates water to Palestinians,” she added. “Israel has been selling water to Palestinians for a long time, but this is enshrining it even further by saying that this is the way to alleviate the water problem.”

Israeli officials say that water problems in the territories could have been addressed had the Palestinians attended the meetings of the joint committee. Palestinians attribute their refusal to conditions set by their counterparts, namely that they must support Israeli settlement water projects for any Palestinian water improvements to be approved.

According to Israeli foreign ministry spokesman Emmanuel Nahshon, “There are many things to be done together to upgrade the water infrastructure in the PA. We are talking about old, leaking pipes, and a more rational use of water.” He also pointed to the illegal tapping into pipes, which he maintained Palestinians did because they did not want to pay for water. “This is something we’ve been wanting to do over the years, and the new water agreement is one of the ways to deal with that. The new agreement … is not only about water quotas; it’s also about more coherent and better use of water, in order to address the needs of the Palestinians.”

But water specialists say that the root cause of the problem is not illegal activity, but the unavailability of water resources to Palestinians and the mismanagement and diversion of the Jordan River.

Access to water is gong to be of increasing urgency should temperatures continue to rise as they have. In many parts of the world, potable water is not easy to find and if temperatures continue to rise areas that did have some water security will lose it and the potential for conflict rises hugely. Palestine and Israel may be a harbinger of what’s to come. As for the commodification of water, I have trouble accepting it; I think everyone has a right to water.

US Dept. of Agriculture announces its nanotechnology research grants

I don’t always stumble across the US Department of Agriculture’s nanotechnology research grant announcements but I’m always grateful when I do as it’s good to find out about  nanotechnology research taking place in the agricultural sector. From a July 21, 2017 news item on Nanowerk,,

The U.S. Department of Agriculture’s (USDA) National Institute of Food and Agriculture (NIFA) today announced 13 grants totaling $4.6 million for research on the next generation of agricultural technologies and systems to meet the growing demand for food, fuel, and fiber. The grants are funded through NIFA’s Agriculture and Food Research Initiative (AFRI), authorized by the 2014 Farm Bill.

“Nanotechnology is being rapidly implemented in medicine, electronics, energy, and biotechnology, and it has huge potential to enhance the agricultural sector,” said NIFA Director Sonny Ramaswamy. “NIFA research investments can help spur nanotechnology-based improvements to ensure global nutritional security and prosperity in rural communities.”

A July 20, 2017 USDA news release, which originated the news item, lists this year’s grants and provides a brief description of a few of the newly and previously funded projects,

Fiscal year 2016 grants being announced include:

Nanotechnology for Agricultural and Food Systems

  • Kansas State University, Manhattan, Kansas, $450,200
  • Wichita State University, Wichita, Kansas, $340,000
  • University of Massachusetts, Amherst, Massachusetts, $444,550
  • University of Nevada, Las Vegas, Nevada,$150,000
  • North Dakota State University, Fargo, North Dakota, $149,000
  • Cornell University, Ithaca, New York, $455,000
  • Cornell University, Ithaca, New York, $450,200
  • Oregon State University, Corvallis, Oregon, $402,550
  • University of Pennsylvania, Philadelphia, Pennsylvania, $405,055
  • Gordon Research Conferences, West Kingston, Rhode Island, $45,000
  • The University of Tennessee,  Knoxville, Tennessee, $450,200
  • Utah State University, Logan, Utah, $450,200
  • The George Washington University, Washington, D.C., $450,200

Project details can be found at the NIFA website (link is external).

Among the grants, a University of Pennsylvania project will engineer cellulose nanomaterials [emphasis mine] with high toughness for potential use in building materials, automotive components, and consumer products. A University of Nevada-Las Vegas project will develop a rapid, sensitive test to detect Salmonella typhimurium to enhance food supply safety.

Previously funded grants include an Iowa State University project in which a low-cost and disposable biosensor made out of nanoparticle graphene that can detect pesticides in soil was developed. The biosensor also has the potential for use in the biomedical, environmental, and food safety fields. University of Minnesota (link is external) researchers created a sponge that uses nanotechnology to quickly absorb mercury, as well as bacterial and fungal microbes from polluted water. The sponge can be used on tap water, industrial wastewater, and in lakes. It converts contaminants into nontoxic waste that can be disposed in a landfill.

NIFA invests in and advances agricultural research, education, and extension and promotes transformative discoveries that solve societal challenges. NIFA support for the best and brightest scientists and extension personnel has resulted in user-inspired, groundbreaking discoveries that combat childhood obesity, improve and sustain rural economic growth, address water availability issues, increase food production, find new sources of energy, mitigate climate variability and ensure food safety. To learn more about NIFA’s impact on agricultural science, visit www.nifa.usda.gov/impacts, sign up for email updates (link is external) or follow us on Twitter @USDA_NIFA (link is external), #NIFAImpacts (link is external).

Given my interest in nanocellulose materials (Canada was/is a leader in the production of cellulose nanocrystals [CNC] but there has been little news about Canadian research into CNC applications), I used the NIFA link to access the table listing the grants and clicked on ‘brief’ in the View column in the University of Pennsylania row to find this description of the project,

ENGINEERING CELLULOSE NANOMATERIALS WITH HIGH TOUGHNESS

NON-TECHNICAL SUMMARY: Cellulose nanofibrils (CNFs) are natural materials with exceptional mechanical properties that can be obtained from renewable plant-based resources. CNFs are stiff, strong, and lightweight, thus they are ideal for use in structural materials. In particular, there is a significant opportunity to use CNFs to realize polymer composites with improved toughness and resistance to fracture. The overall goal of this project is to establish an understanding of fracture toughness enhancement in polymer composites reinforced with CNFs. A key outcome of this work will be process – structure – fracture property relationships for CNF-reinforced composites. The knowledge developed in this project will enable a new class of tough CNF-reinforced composite materials with applications in areas such as building materials, automotive components, and consumer products.The composite materials that will be investigated are at the convergence of nanotechnology and bio-sourced material trends. Emerging nanocellulose technologies have the potential to move biomass materials into high value-added applications and entirely new markets.

It’s not the only nanocellulose material project being funded in this round, there’s this at North Dakota State University, from the NIFA ‘brief’ project description page,

NOVEL NANOCELLULOSE BASED FIRE RETARDANT FOR POLYMER COMPOSITES

NON-TECHNICAL SUMMARY: Synthetic polymers are quite vulnerable to fire.There are 2.4 million reported fires, resulting in 7.8 billion dollars of direct property loss, an estimated 30 billion dollars of indirect loss, 29,000 civilian injuries, 101,000 firefighter injuries and 6000 civilian fatalities annually in the U.S. There is an urgent need for a safe, potent, and reliable fire retardant (FR) system that can be used in commodity polymers to reduce their flammability and protect lives and properties. The goal of this project is to develop a novel, safe and biobased FR system using agricultural and woody biomass. The project is divided into three major tasks. The first is to manufacture zinc oxide (ZnO) coated cellulose nanoparticles and evaluate their morphological, chemical, structural and thermal characteristics. The second task will be to design and manufacture polymer composites containing nano sized zinc oxide and cellulose crystals. Finally the third task will be to test the fire retardancy and mechanical properties of the composites. Wbelieve that presence of zinc oxide and cellulose nanocrystals in polymers will limit the oxygen supply by charring, shielding the surface and cellulose nanocrystals will make composites strong. The outcome of this project will help in developing a safe, reliable and biobased fire retardant for consumer goods, automotive, building products and will help in saving human lives and property damage due to fire.

One day, I hope to hear about Canadian research into applications for nanocellulose materials. (fingers crossed for good luck)

2017 Research as Art Awards at Swansea University (UK)

It’s surprising I haven’t stumbled across Swansea University’s (UK) Research as Art competitions before now. still, I’m happy to have done so now.

Picture: Research as Art winner 2017. “Bioblocks: building for nature”. How the tidal lagoon could be a habitat for marine creatures.

A July 14, 2017 news item on phys.org announces the results of 2017 Research as Art competition,

Fifteen stunning images, and the fascinating stories behind them—such as how a barn owl’s pellets reveal which animals it has eaten, how data can save lives, and how Barbie breaks free—have today been revealed as the winners of the 2017 Research as Art awards.

The overall winner is Dr Ruth Callaway, a research officer from the College of Science. Her entry, Bioblocks: building for nature, illustrates how children and researchers have been exploring ways in which the tidal lagoon proposed for Swansea Bay could become a new habitat for marine creatures.

A July 14, 2017 Swansea University press release, which originated the news item, describes the competition in more detail (Note: Links have been removed),

Research as Art is the only competition of its kind, open to researchers from all subjects, and with an emphasis on telling the research story, as well as composing a striking image.

It offers an outlet for researchers’ creativity, and celebrates the diversity, beauty, and impact of research at Swansea University – a top 30 research university.

86 entries were received from researchers across all Colleges of the University.

A distinguished judging panel of senior figures selected a total of fifteen winners. Along with the overall winner, there were judges’ awards in four categories relating to engagement – imagination, inspiration, illumination, and the natural world – and 10 highly-commended entries.

Judging panel:

Prof. Gail Cardew – Professor of Science, Culture and Society at the Royal Institution
Dan Cressey, Reporter, Nature News
Flora Graham – Digital Editor of NewScientist
Barbara Kiser, Books and Arts Editor, Nature

Overall winner Dr Ruth Callaway described the image in her winning entry:

“Over 200 children used cubes of clay to sculpt ecologically attractive habitats for coastal creatures. These bioblocks demonstrate that humanmade structures can support marine life, while children and their families have gained a better understanding of the unique resilience of sea creatures.

It is hoped that the diverse and complex habitat will enable more species to use this new material as a living space: crevices and holes will provide shelter; variable textures and overhangs will allow animals and seaweed to cling to the material.”

Dr Ruth Callaway added:

“Innovative projects such as the Tidal Lagoon Swansea Bay are inspiring, but they also throw up lots of questions and complex environmental challenges.

For marine scientists, the project creates unprecedented research opportunities to explore how the construction process could reduce negative impact on the coastal environment.

The EU-funded SEACAMS project and the company Tidal Lagoon Power work in collaboration, and we explore novel ways of enhancing biodiversity. Discussing these ideas with the public both informs the wider community about our work and triggers new research ideas.”

Competition founder and Director Dr Richard Johnston, Associate Professor in materials science and engineering at Swansea University, said:

“Research as Art is an opportunity for researchers to reveal hidden aspects of their research to audiences they wouldn’t normally engage with. This may uncover their personal story, their humanity, their inspiration, and emotion.

It can also be a way of presenting their research process, and what it means to be a researcher; fostering dialogue, and dissolving barriers between universities and the wider world.”

You can find out more about the competition, which seems to date from 2012, on the Research as Art competition page and more about the SEACAMS project here.

The US White House and its Office of Science and Technology Policy (OSTP)

It’s been a while since I first wrote this but I believe this situation has not changed.

There’s some consternation regarding the US Office of Science and Technology Policy’s (OSTP) diminishing size and lack of leadership. From a July 3, 2017 article by Bob Grant for The Scientist (Note: Links have been removed),

Three OSTP staffers did leave last week, but it was because their prearranged tenures at the office had expired, according to an administration official familiar with the situation. “I saw that there were some tweets and what-not saying that it’s zero,” the official tells The Scientist. “That is not true. We have plenty of PhDs that are still on staff that are working on science. All of the work that was being done by the three who left on Friday had been transitioned to other staffers.”

At least one of the tweets that the official is referring to came from Eleanor Celeste, who announced leaving OSTP, where she was the assistant director for biomedical and forensic sciences. “science division out. mic drop,” she tweeted on Friday afternoon.

The administration official concedes that the OSTP is currently in a state of “constant flux” and at a “weird transition period” at the moment, and expects change to continue. “I’m sure that the office will look even more different in three months than it does today, than it did six months ago,” the official says.

Jeffrey Mervis in two articles for Science Magazine is able to provide more detail. From his July 11, 2017 article,

OSTP now has 35 staffers, says an administration official who declined to be named because they weren’t authorized to speak to the media. Holdren [John Holdren], who in January [2017] returned to Harvard University, says the plunge in staff levels is normal during a presidential transition. “But what’s shocking is that, this far into the new administration, the numbers haven’t gone back up.”

The office’s only political appointee is Michael Kratsios, a former aide to Trump confidant and Silicon Valley billionaire Peter Thiel. Kratsios is serving as OSTP’s deputy chief technology officer and de facto OSTP head. Eight new detailees have arrived from other agencies since the inauguration.

Although there has been no formal reorganization of OSTP, a “smaller, more collaborative staff” is now grouped around three areas—science, technology, and national security—according to the Trump aide. Three holdovers from Obama’s OSTP are leading teams focused on specific themes—Lloyd Whitman in technology, Chris Fall in national security, and Deerin Babb-Brott in environment and energy. They report to Kratsios and Ted Wackler, a career civil servant who was Holdren’s deputy chief of staff and who joined OSTP under former President George W. Bush.

“It’s a very flat structure,” says the Trump official, consistent with the administration’s view that “government should be looking for ways to do more with less.” Ultimately, the official adds, “the goal is [for OSTP] to have “probably closer to 50 [people].”

A briefing book prepared by Obama’s outgoing OSTP staff may be a small but telling indication of the office’s current status. The thick, three-ring binder, covering 100 issues, was modeled on one that Holdren received from John “Jack” Marburger, Bush’s OSTP director. “Jack did a fabulous job of laying out what OSTP does, including what reports it owes Congress, so we decided to do likewise,” Holdren says. “But nobody came [from Trump’s transition team] to collect it until a week before the inauguration.”

That person was Reed Cordish, the 43-year-old scion of billionaire real estate developer David Cordish. An English major in college, Reed Cordish was briefly a professional tennis player before joining the family business. He “spent an hour with us and took the book away,” Holdren says. “He told us, ‘This is an important operation and I’ll do my best to see that it flourishes.’ But we don’t know … whether he has the clout to make that happen.”

Cordish is now assistant to the president for intragovernmental and technology initiatives. He works in the new Office of American Innovation led by presidential son-in-law Jared Kushner. That office arranged a recent meeting with high-tech executives, and is also leading yet another White House attempt to “reinvent” government.

Trump has renewed the charter of the National Science and Technology Council, a multiagency group that carries out much of the day-to-day work of advancing the president’s science initiatives. … Still pending is the status of the President’s Council of Advisors on Science and Technology [emphasis mine], a body of eminent scientists and high-tech industry leaders that went out of business at the end of the Obama administration.

Mervis’ July 12, 2017 article is in the form of a Q&A (question and answer) session with the previously mentioned John Holdren, director of the OSTP in Barack Obama’s administration,

Q: Why did you have such a large staff?

A: One reason was to cover the bases. We knew from the start that the Obama administration thought cybersecurity would be an important issue and we needed to be capable in that space. We also knew we needed people who were capable in climate change, in science and technology for economic recovery and job creation and sustained economic growth, and people who knew about advanced manufacturing and nanotechnology and biotechnology.

We also recruited to carry out specific initiatives, like in precision medicine, or combating antibiotic resistance, or the BRAIN [Brain Research through Advancing Innovative Neurotechnologies] initiative. Most of the work will go on in the departments and agencies, but you need someone to oversee it.

The reason we ended up with 135 people at our peak, which was twice the number during its previous peak in the Clinton administration’s second term, was that this president was so interested in knowing what science could do to advance his agenda, on economic recovery, or energy and climate change, or national intelligence. He got it. He didn’t need to be tutored on why science and technology matters.

I feel I’ve been given undue credit for [Obama] being a science geek. It wasn’t me. He came that way. He was constantly asking what we could do to move the needle. When the first flu epidemic, H1N1, came along, the president immediately turned to me and said, “OK, I want [the President’s Council of Advisors on Science and Technology] to look in depth on this, and OSTP, and NIH [National Institutes of Health], and [the Centers for Disease Control and Prevention].” And he told us to coordinate my effort on this stuff—inform me on what can be done and assemble the relevant experts. It was the same with Ebola, with the Macondo oil spill in the Gulf, with Fukushima, where the United States stepped up to work with the Japanese.

It’s not that we had all the expertise. But our job was to reach out to those who did have the relevant expertise.

Q: OSTP now has 35 people. What does that level of staffing say to you?

A: I have to laugh.

Q: Why?

A: When I left, on 19 January [2017], we were down to 30 people. And a substantial fraction of the 30 were people who, in a sense, keep the lights on. They were the OSTP general counsel and deputy counsel, the security officer and deputy, the budget folks, the accounting folks, the executive director of NSTC [National Science and Technology Council].

There are some scientists left, and there are some scientists there still. But on 30 June the last scientist in the science division left.

Somebody said OSTP has shut down. But that’s not quite it. There was no formal decision to shut anything down. But they did not renew the contract of the last remaining science folks in the science division.

I saw somebody say, “Well, we still have some Ph.D.s left.” And that’s undoubtedly true. There are still some science Ph.D.s left in the national security and international affairs division. But because [OSTP] is headless, they have no direct connection to the president and his top advisers.

I don’t want to disparage the top people there. The top people there now are Michael Kratsios, who they named the deputy chief technology officer, and Ted Wackler, who was my deputy chief of staff and who was [former OSTP Director] Jack Marberger’s deputy, and who I kept because he’s a fabulously effective manager. And I believe that they are doing everything they can to make sure that OSTP, at the very least, does the things it has to do. … But right now I think OSTP is just hanging on.

Q: Why did some people choose to stay on?

A: A large portion of OSTP staff are borrowed from other agencies, and because the White House is the White House, we get the people we need. These are dedicated folks who want to get the job done. They want to see science and technology applied to advance the public interest. And they were willing to stay and do their best despite the considerable uncertainty about their future.

But again, most of the detailees, and the reason we went from 135 to 30 almost overnight, is that it’s pretty standard for the detailees to go back to their home agencies and wait for the next administration to decide what set of detailees it wants to advance their objects.

So there’s nothing shocking that most of the detailees went back to their home agencies. The people who stayed are mostly employed directly by OSTP. What’s shocking is that, this far into the new administration, that number hasn’t gone back up. That is, they have only five more people than they had on January 20 [2017].

As I had been wondering about the OSTP and about the President’s Council of Advisors on Science and Technology (PCAST), it was good to get an update.

On a more parochial note, we in Canada are still waiting for an announcement about who our Chief Science Advisor might be.

Cryopreserving and reviving fish embryos

Cryopreservation and the promise of animal revivification is not one of my favourite topics, from a July 13, 2017 news item on Nanowerk (Note: A link has been removed),

Scientists report for the first time the ability to both deep freeze and reanimate zebrafish embryos. The method, appearing in the journal ACS Nano (“Gold Nanorod Induced Warming of Embryos from the Cryogenic State Enhances Viability”), could potentially be used to bank larger aquatic and other vertebrate oocytes and embryos, too, for a life in the future.

It seems the science is more advanced than I’d realized. A July 13, 2017 American Chemical Society news release on EurekAlert, which originated the news item, describes cryopreservation and the technique the scientists used,

Cryopreservation has been used to save sperm, oocytes and even embryos of many species, including humans, cattle and lab animals. Preserving the embryos of most fishes, however, has remained an elusive goal. The embryos are relatively large with big yolks and are divided by multiple compartments. These traits make the embryos difficult to cool and warm uniformly without damage and ice formation. A few techniques, including microinjection of cryoprotectants and laser irradiation for re-warming, have shown promise toward achieving this long-sought goal. John Bischof and colleagues wanted to tweak the methods to see if they could finally make cryopreserving fish a reality.

The researchers injected a cryoprotectant, along with plasmonic gold nanoparticles to serve as a laser absorber, directly into zebrafish embryos. Plunging the embryos in liquid nitrogen rapidly cooled them to a cryogenically stable state in less than a second, according to modeling results. The researchers then used laser irradiation to heat up the nanoparticles, which were uniformly distributed inside the embryos, at an ultra-fast rate (1.4 x 107 degrees Celsius per minute). Not all of the embryos made it, but many were revived –a feat that is currently not possible by other techniques. Their hearts, eyes and nervous systems developed through at least the next 28 hours — and they started to wiggle. As more fish populations shrink and become threatened, the researchers say the cryopreservation method could help establish banks of frozen fish germ cells and embryos that could one day help replenish the oceans’ biodiversity. The technique could also be applied to amphibian, reptile and bird species with similar embryonic sizes and structures.

Here’s a video describing the work,

After watching that a video, I feel that I should revise my opinion of cryopreservation,

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

Gold Nanorod Induced Warming of Embryos from the Cryogenic State Enhances Viability by Kanav Khosla, Yiru Wang, Mary Hagedorn, Zhenpeng Qin, and John Bischof. ACS Nano, Article ASAP DOI: 10.1021/acsnano.7b02216 Publication Date (Web): July 13, 2017

Copyright © 2017 American Chemical Society

This paper is behind a paywall.

Tiger escapes from an impenetrable cage—carbon atoms show quantum effects

The likelihood of a tiger escaping from a cage using quantum effects is incredibly small. Things seem quite different for carbon. © Fotolia, Bubbers

I’ll get to the tiger reference in a moment, first, here’s a July 12, 2017 news item on Nanowerk announcing the research that inspired the tiger reference (Note A link has been removed),

Chemists at Ruhr-Universität Bochum have found evidence that carbon atoms cannot only behave like particles but also like waves. This quantum-mechanical property is well-known for light particles such as electrons or hydrogen atoms. However, researchers have only rarely observed the wave-particle duality for heavy atoms, such as carbon.

The team led by Prof Dr Wolfram Sander and Tim Schleif from the Chair for Organic Chemistry II together with Prof Dr Weston Thatcher Borden, University of North Texas, reports in the journal Angewandte Chemie (“The Cope rearrangement of 1,5-Dimethylsemibullvalene-2(4)-d1: Experimental evidence for heavy-atom tunneling”).

“Our result is one of few examples showing that carbon atoms can display quantum effects,” says Sander. Specifically, the researchers observed that carbon atoms can tunnel. They thus overcome an energetic barrier, although they do not actually possess enough energy to do that.

A July 12, 2017 Ruhr-Universität Bochum press release (also on EurekAlert), which originated the news item, expands on the theme and makes sense of the tiger analogy,

Wolfram Sander explains the paradox: “It’s as though a tiger has left his cage without jumping over the fence, which is much too high for him. But he still gets out.” This is only possible if he behaves like a wave, but not if he behaves like a particle. The probability of an object being able to tunnel depends on its mass. The phenomenon can, for instance, be observed much more easily for light electrons than for relatively heavy carbon atoms.

The researchers investigated the tunnel reaction using the Cope rearrangement, a chemical reaction that has been known for almost 80 years. The starting material for the reaction, a hydrocarbon compound, is identical to the product molecule. The same chemical compound thus exists before and after the reaction. However, the bonds between the carbon atoms change during the process.

In their experiment, the Bochum-based researchers marked one of the carbon atoms in the molecule: They replaced the hydrogen atom bonded to it with the hydrogen isotope deuterium, a heavier version of hydrogen. Molecules before and after the Cope rearrangement differed in terms of the distribution of the deuterium. Due to these different distributions, both molecular forms had slightly different energies.

Reaction shouldn’t actually take place

At room temperature, this difference has little effect; due to the plentiful supply of thermal energy in the surrounding area, both forms occur equally frequently. However, at very low temperatures under ten Kelvin, one molecule form is significantly preferred due to the energy difference. When transitioning from room temperature to extremely low temperatures, the balance has to move from an equal distribution of both forms to an uneven distribution.

This transition cannot, however, occur in the classic way – since, when rearranging from one form to the other, an energy barrier has to be overcome, although the molecule itself does not have the energy for this and the cold environment is also unable to provide it. Although the new balance should not occur in the classic way, the researchers were nevertheless able to demonstrate it in the experiment. Their conclusion: the Cope rearrangement at extremely low temperatures can only be explained by a tunnel effect. They thus provided experimental evidence for a prediction made by Weston Borden over five years ago based on theoretical studies.

Solvents influence ability to tunnel

At Ruhr-Universität, Wolfram Sander undertakes research in the cluster of excellence Ruhr Explores Solvation, where he concerns himself with the interactions of solvents and dissolved molecules. “It is known that solvents influence the ability to tunnel,” says the chemist. “However, so far it has not been understood how they do that.”

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

The Cope rearrangement of 1,5-Dimethylsemibullvalene-2(4)-d1: Experimental evidence for heavy-atom tunneling by Tim Schleif, Joel Mieres-Perez, Stefan Henkel, Melanie Ertelt, Weston Thatcher Borden, Wolfram Sander. Angewandte Chemie, 2017, DOI: 10.1002/ange.201704787, International Edition: 10.1002/anie.201704787

This paper is behind a paywall.

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.

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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