Shape-conforming hydrogel and the body’s own healing mechanisms

A June 11, 2018 news item on ScienceDaily announces a development of interest to people with diabetes or those who treat them,

A simple scrape or sore might not cause alarm for most people. But for diabetic patients, an untreated scratch can turn into an open wound that could potentially lead to a limb amputation or even death.

A Northwestern University team has developed a new device, called a regenerative bandage, that quickly heals these painful, hard-to-treat sores without using drugs. During head-to-head tests, Northwestern’s bandage healed diabetic wounds 33 percent faster than one of the most popular bandages currently on the market.

A June 11, 2018 Northwestern University news release by Amanda Morris, which originated the news item, provides more detail,

“The novelty is that we identified a segment of a protein in skin that is important to wound healing, made the segment and incorporated it into an antioxidant molecule that self-aggregates at body temperature to create a scaffold that facilitates the body’s ability to regenerate tissue at the wound site,” said Northwestern’s Guillermo Ameer, who led the study. “With this newer approach, we’re not releasing drugs or outside factors to accelerate healing. And it works very well.”

Because the bandage leverages the body’s own healing power without releasing drugs or biologics, it faces fewer regulatory hurdles. This means patients could see it on the market much sooner.

The research was published today, June 11 [2018], in the Proceedings of the National Academy of Sciences. Although Ameer’s laboratory is specifically interested in diabetes applications, the bandage can be used to heal all types of open wounds.

An expert in biomaterials and regenerative engineering, Ameer is the Daniel Hale Williams Professor of Biomedical Engineering in the McCormick School of Engineering, professor of surgery in the Feinberg School of Medicine and director of Northwestern’s new Center for Advanced Regenerative Engineering (CARE).

The difference between a sore in a physically healthy person versus a diabetic patient? Diabetes can cause nerve damage that leads to numbness in the extremities. People with diabetes, therefore, might experience something as simple as a blister or small scratch that goes unnoticed and untreated because they cannot feel it to know it’s there. As high glucose levels also thicken capillary walls, blood circulation slows, making it more difficult for these wounds to heal. It’s a perfect storm for a small nick to become a limb-threatening — or life-threatening — wound.

The secret behind Ameer’s regenerative bandage is laminin, a protein found in most of the body’s tissues including the skin. Laminin sends signals to cells, encouraging them to differentiate, migrate and adhere to one another. Ameer’s team identified a segment of laminin — 12 amino acids in length — called A5G81 that is critical for the wound-healing process.

“This particular sequence caught our eye because it activates cellular receptors to get cells to adhere, migrate and proliferate,” Ameer said. “Then we cut up the sequence to find the minimum size that we needed for it to work.”

By using such a small fragment of laminin rather than the entire protein, it can be easily synthesized in the laboratory — making it more reproducible while keeping manufacturing costs low. Ameer’s team incorporated A5G81 into an antioxidant hydrogel bandage that it previously developed in the laboratory.

The bandage’s antioxidant nature counters inflammation. And the hydrogel is thermally responsive: It is a liquid when applied to the wound bed, then rapidly solidifies into a gel when exposed to body temperature. This phase change allows it to conform to the exact shape of the wound — a property that helped it out-perform other bandages on the market.

“Wounds have irregular shapes and depths. Our liquid can fill any shape and then stay in place,” Ameer said. “Other bandages are mostly based on collagen films or sponges that can move around and shift away from the wound site.”

Patients also must change bandages often, which can rip off the healing tissue and re-injure the site. Ameer’s bandage, however, can be rinsed off with cool saline, so the regenerating tissue remains undisturbed.

Not only will the lack of drugs or biologics make the bandage move to market faster, it also increases the bandage’s safety. So far, Ameer’s team has not noticed any adverse side effects in animal models. This is a stark difference from another product on the market, which contains a growth factor linked to cancer.

“It is not acceptable for patients who are trying to heal an open sore to have to deal with an increased risk of cancer,” Ameer said.

Next, Ameer’s team will continue to investigate the bandage in a larger pre-clinical model.

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

Potent laminin-inspired antioxidant regenerative dressing accelerates wound healing in diabetes by Yunxiao Zhu, Zdravka Cankova, Marta Iwanaszko, Sheridan Lichtor, Milan Mrksich, and Guillermo A. Ameer. PNAS [Proceedings of the National Academy of Science] June 11, 2018. 201804262; published ahead of print June 11, 2018. https://doi.org/10.1073/pnas.1804262115

This paper is behind a paywall.

Australian scientists say that sunscreens with zinc oxide nanoparticles aren’t toxic to you

The Australians have had quite the struggle over whether or not to use nanotechnology-enabled sunscreens (see my Feb. 9, 2012 posting about an Australian nanosunscreen debacle and I believe the reverberations continue even ’til today). This latest research will hopefully help calm the waters. From a Dec. 4, 2018 news item on ScienceDaily,

Zinc oxide (ZnO) has long been recognized as an effective sunscreen agent. However, there have been calls for sunscreens containing ZnO nanoparticles to be banned because of potential toxicity and the need for caution in the absence of safety data in humans. An important new study provides the first direct evidence that intact ZnO nanoparticles neither penetrate the human skin barrier nor cause cellular toxicity after repeated application to human volunteers under in-use conditions. This confirms that the known benefits of using ZnO nanoparticles in sunscreens clearly outweigh the perceived risks, reports the Journal of Investigative Dermatology.

A December 4, 2018 Elsevier (Publishing) press release (also on EurekAlert), which originated the news item, provides international context for the safety discussion while providing more details about this latest research,

The safety of nanoparticles used in sunscreens has been a highly controversial international issue in recent years, as previous animal exposure studies found much higher skin absorption of zinc from application of ZnO sunscreens to the skin than in human studies. Some public advocacy groups have voiced concern that penetration of the upper layer of the skin by sunscreens containing ZnO nanoparticles could gain access to the living cells in the viable epidermis with toxic consequences, including DNA damage. A potential danger, therefore, is that this concern may also result in an undesirable downturn in sunscreen use. A 2017 National Sun Protection Survey by the Cancer Council Australia found only 55 percent of Australians believed it was safe to use sunscreen every day, down from 61 per cent in 2014.

Investigators in Australia studied the safety of repeated application of agglomerated ZnO nanoparticles applied to five human volunteers (aged 20 to 30 years) over five days. This mimics normal product use by consumers. They applied ZnO nanoparticles suspended in a commercial sunscreen base to the skin of volunteers hourly for six hours and daily for five days. Using multiphoton tomography with fluorescence lifetime imaging microscopy, they showed that the nanoparticles remained within the superficial layers of the stratum corneum and in the skin furrows. The fate of ZnO nanoparticles was also characterized in excised human skin in vitro. They did not penetrate the viable epidermis and no cellular toxicity was seen, even after repeated hourly or daily applications typically used for sunscreens.

“The terrible consequences of skin cancer and photoaging are much greater than any toxicity risk posed by approved sunscreens,” stated lead investigator Michael S. Roberts, PhD, of the Therapeutics Research Centre, The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, and School of Pharmacy and Medical Sciences, University of South Australia, Sansom Institute, Adelaide, QLD, Australia.

“This study has shown that sunscreens containing nano ZnO can be repeatedly applied to the skin with minimal risk of any toxicity. We hope that these findings will help improve consumer confidence in these products, and in turn lead to better sun protection and reduction in ultraviolet-induced skin aging and cancer cases,” he concluded.

“This study reinforces the important public health message that the known benefits of using ZnO nano sunscreens clearly outweigh the perceived risks of using nano sunscreens that are not supported by the scientific evidence,” commented Paul F.A. Wright, PhD, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia, in an accompanying editorial. “Of great significance is the investigators’ finding that the slight increase in zinc ion concentrations in viable epidermis was not associated with cellular toxicity under conditions of realistic ZnO nano sunscreen use.

A November 21, 2018 University of South Australia press release (also on EurekAlert) provides some additional insight into the Australian situation,, Note: Links have been removed,

It’s safe to slap on the sunscreen this summer – in repeated doses – despite what you have read about the potential toxicity of sunscreens.

A new study led by the University of Queensland (UQ) and University of South Australia (UniSA) provides the first direct evidence that zinc oxide nanoparticles used in sunscreen neither penetrate the skin nor cause cellular toxicity after repeated applications.

The research, published this week in the Journal of Investigative Dermatology, refutes widespread claims among some public advocacy groups – and a growing belief among consumers – about the safety of nanoparticulate-based sunscreens.

UQ and UniSA lead investigator, Professor Michael Roberts, says the myth about sunscreen toxicity took hold after previous animal studies found much higher skin absorption of zinc-containing sunscreens than in human studies.

“There were concerns that these zinc oxide nanoparticles could be absorbed into the epidermis, with toxic consequences, including DNA damage,” Professor Roberts says.

The toxicity link was picked up by consumers, sparking fears that Australians could reduce their sunscreen use, echoed by a Cancer Council 2017 National Sun Protection Survey showing a drop in the number of people who believed it was safe to use sunscreens every day.

Professor Roberts and his co-researchers in Brisbane, Adelaide, Perth and Germany studied the safety of repeated applications of zinc oxide nanoparticles applied to five volunteers aged 20-30 years.

Volunteers applied the ZnO nanoparticles every hour for six hours on five consecutive days.

“Using superior imaging methods, we established that the nanoparticles remained within the superficial layers of the skin and did not cause any cellular damage,” Professor Roberts says.

“We hope that these findings help improve consumer confidence in these products and in turn lead to better sun protection. The terrible consequences of skin cancer and skin damage caused by prolonged sun exposure are much greater than any toxicity posed by approved sunscreens.”

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

Support for the Safe Use of Zinc Oxide Nanoparticle Sunscreens: Lack of Skin Penetration or Cellular Toxicity after Repeated Application in Volunteers by Yousuf H. Mohammed, Amy Holmes, Isha N. Haridass, Washington Y. Sanchez, Hauke Studier, Jeffrey E. Grice, Heather A.E. Benson, Michael S. Roberts. Jurnal of Investigative Dermatology. DOI: https://doi.org/10.1016/j.jid.2018.08.024 Article in Press Published online (Dec. 4, 2018?)

As of Dec. 11, 2018, this article is open access.

Nanostructured materials and radiation

If you’re planning on using nanostructured materials in a nuclear facility, you might want to check out this work (from a June 8, 2018 Purdue University (Indiana, US) news release by Brian L. Huchel,

A professor in the Purdue College of Engineering examined the potential use of various materials in nuclear reactors in an extensive review article in the journal Progress in Materials Science.

The article, titled “Radiation Damage in Nanostructured Materials,” was led by Xinghang Zhang, a professor of materials engineering. It will be published in the July issue of the journal.

Zhang said there is a significant demand for advanced materials that can survive high temperature and high doses of radiation. These materials contain significant amount of internal changes, called defect sinks, which are too small to be seen with the naked eye, but may form the next generation of materials used in nuclear reactors.

“Nanostructured materials with abundant internal defect sinks are promising as these materials have shown significantly improved radiation tolerance,” he said. “However, there are many challenges and fundamental science questions that remain to be solved before these materials can have applications in advanced nuclear reactors.”

The 100-page article, which took two years to write, focuses on metallic materials and metal-ceramic compounds and reviews types of internal material defects on the reduction of radiation damage in nanostructured materials.

Under the extreme radiation conditions, a large number of defects and their clusters are generated inside materials, and such significant microstructure damage often leads to degradation of the mechanical and physical properties of the materials

The article discusses the usage of a combination of defect sink networks to collaboratively improve the radiation tolerance of nanomaterials, while pointing out the need to improve the thermal and radiation stabilities of the defect sinks.

“The field of radiation damage in nanostructured materials is an exciting and rapidly evolving arena, enriched with challenges and opportunities,” Zhang said. “The integration of extensive research effort, resources and expertise in various fields may eventually lead to the design of advanced nanomaterials with unprecedented radiation tolerance.”

Jin Li, co-author of the review article and a postdoctoral fellow in the School of Materials Engineering, said researchers with different expertise worked collaboratively on the article, which contains more than 100 pages, 100 figures and 700 references.

The team involved in the research article included researchers from Purdue, Texas A&M University, Drexel University, the University of Nebraska-Lincoln and China University of Petroleum-Beijing, as well as Sandia National Laboratory, Los Alamos National Laboratory and Idaho National Laboratory.

Here’s an image illustrating the work,

Various imperfections in nanostructures, call defect sinks, can enhance the material’s tolerance to radiation. (Photo/Xinghang Zhang)

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

Radiation damage in nanostructured materials by Xinghang Zhang, Khalid Hattar, Youxing Chen, Lin Shao, Jin Li, Cheng Sun, Kaiyuan Yu, Nan Li, Mitra L.Taheri, Haiyan Wang, Jian Wang, Michael Nastasi. Progress in Materials Science Volume 96, July 2018, Pages 217-321 https://doi.org/10.1016/j.pmatsci.2018.03.002

This paper is behind a paywall.

ht/ to June 8, 2018 Nanowerk news item.

Nano-saturn

It’s a bit of a stretch but I really appreciate how the nanoscale (specifically a fullerene) is being paired with the second largest planet (the largest is Jupiter) in our solar system. (See Nola Taylor Redd’s November 14, 2012 article on space.com for more about the planet Saturn.)

From a June 8, 2018 news item on ScienceDaily,

Saturn is the second largest planet in our solar system and has a characteristic ring. Japanese researchers have now synthesized a molecular “nano-Saturn.” As the scientists report in the journal Angewandte Chemie, it consists of a spherical C(60) fullerene as the planet and a flat macrocycle made of six anthracene units as the ring. The structure is confirmed by spectroscopic and X-ray analyses.

A June 8, 2018  Wiley Publications press release (also on EurekAlert), which originated the news item, fills in some details,

Nano-Saturn systems with a spherical molecule and a macrocyclic ring have been a fascinating structural motif for researchers. The ring must have a rigid, circular form, and must hold the molecular sphere firmly in its midst. Fullerenes are ideal candidates for the nano-sphere. They are made of carbon atoms linked into a network of rings that form a hollow sphere. The most famous fullerene, C60, consists of 60 carbon atoms arranged into 5- and 6-membered rings like the leather patches of a classic soccer ball. The electrons in their double bonds, knows as the π-electrons, are in a kind of “electron cloud”, able to freely move about and have binding interactions with other molecules, such as a macrocycle that also has a “cloud” of π-electrons. The attractive interactions between the electron clouds allow fullerenes to lodge in the cavities of such macrocycles.

A series of such complexes has previously been synthesized. Because of the positions of the electron clouds around the macrocycles, it was previously only possible to make rings that surround the fullerene like a belt or a tire. The ring around Saturn, however, is not like a “belt” or “tire”, it is a very flat disc. Researchers working at the Tokyo Institute of Technology and Okayama University of Science (Japan) wanted to properly imitate this at nanoscale.

Their success resulted from a different type of bonding between the “nano-planet” and its “nano-ring”. Instead of using the attraction between the π-electron clouds of the fullerene and macrocycle, the team working with Shinji Toyota used the weak attractive interactions between the π-electron cloud of the fullerene and non- π-electron of the carbon-hydrogen groups of the macrocycle.

To construct their “Saturn ring”, the researchers chose to use anthracene units, molecules made of three aromatic six-membered carbon rings linked along their edges. They linked six of these units into a macrocycle whose cavity was the perfect size and shape for a C60 fullerene. Eighteen hydrogen atoms of the macrocycle project into the middle of the cavity. In total, their interactions with the fullerene are enough to give the complex enough stability, as shown by computer simulations. By using X-ray analysis and NMR spectroscopy, the team was able to prove experimentally that they had produced Saturn-shaped complexes.

Here’s an illustration of the ‘nano-saturn’,

Courtesy: Wiley Publications

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

Nano‐Saturn: Experimental Evidence of Complex Formation of an Anthracene Cyclic Ring with C60 by Yuta Yamamoto, Dr. Eiji Tsurumaki, Prof. Dr. Kan Wakamatsu, Prof. Dr. Shinji Toyota. Angewandte Chemie https://doi.org/10.1002/anie.201804430 First published: 30 May 2018

This paper is behind a paywall.

Therapeutic nanoparticles for agricultural crops

Nanoscale drug delivery systems developed by the biomedical community may prove useful to farmers. The Canadian Broadcasting Corporation (CBC) featured the story in a May 26, 2018 online news item (with audio file; Note: A link has been removed),

Thanks to a fortuitous conversation between an Israeli chemical engineer who works on medical nanotechnology and his farmer friend, there’s a new way to deliver nourishment to nutrient-starved crops.

Avi Schroeder, the chemical engineer and cancer researcher from Technion — Israel Institute of Technology asked his friend what are the major problems facing agriculture today. “He said, ‘You know Avi, one of the major issues we’re facing is that in some of the crops we try to grow, we actually have a lack of nutrients. And then we end up not growing those crops even though they’re very valuable or very important crops.'”

This problem is only going to become more acute in many regions of the world as global population approaches eight billion people.

“Feeding them with healthy food and nutritious food is becoming a major limiting factor. And … the land we can actually grow crops on are also becoming smaller and smaller in every country because people need to build houses too. So what we want is to get actually more crops per hectare.”

The way farmers currently deliver nutrients to malnourished agricultural crops is very inefficient. Much of what is added to the leaves of the plant is wasted. Most of it washes away or isn’t taken up by the plants.

If plants don’t get the nutrients they need, their leaves start to yellow, their growth becomes stunted and they don’t produce as much food as nutrient-rich crops.

“We work primarily in the field of medicine,” says Schroeder. “What we do many times is we’ll load minuscule doses of medicine into nanoparticles — we’ll inject them into the patient. And those nanoparticles will actually be able to detect the disease site inside the body. That sounded very, very similar to the problem the farmers were actually facing — how do you get a medicine into a crop or a nutrient into a crop and get it to the right region within the crop where it’s actually necessary.”

The nanoparticles Schroeder developed are tiny packages that can deliver nutrients — any nutrients — that are placed inside.

A June 6, 2018 news item on Nanowerk offers a few more details,

An innovative technology developed at the Technion [Israel Institute of Technology] could lead to significant increases in agricultural yields. Using a nanometric transport platform on plants that was previously utilized for targeted drug delivery, researchers increased the penetration rate of nutrients into the plants, from 1% to approximately 33%.

A May 27,2018 Technion press release, which originated the news item, fleshes out the details,

The technology exploits nanoscale delivery platforms which until now were used to transport drugs to specific targets in the patient’s body. The work was published in Scientific Reports and will be presented in Nature Press.

The use of the nanotechnology for targeted drug delivery has been the focus of research activity conducted at the Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies at the Wolfson Faculty of Chemical Engineering. The present research repurposes this technology for agricultural use; and is being pursued by laboratory director Prof. Avi Schroeder and graduate student Avishai Karny.

“The constant growth in the world population demands more efficient agricultural technologies, which will produce greater supplies of healthier foods and reduce environmental damage,” said Prof. Schroeder. “The present work provides a new means of delivering essential nutrients without harming the environment.”

The researchers loaded the nutrients into liposomes which are small spheres generated in the laboratory, comprised of a fatty outer layer enveloping the required nutrients. The particles are stable in the plant’s aqueous environment and can penetrate the cells. In addition, the Technion researchers can ‘program’ them to disintegrate and release the load at precisely the location and time of interest, namely, in the roots and leaves. Disintegration occurs in acidic environments or in response to an external signal, such as light waves or heat. The molecules comprising the particles are derived from soy plants and are therefore approved and safe for consumption by both humans and animals.

In the present experiment, the researchers used 100-nanometer liposomes to deliver the nutrients iron and magnesium into both young and adult tomato crops. They demonstrated that the liposomes, which were sprayed in the form of a solution onto the leaves, penetrated the leaves and reached other leaves and roots. Only when reaching the root cells did they disintegrate and release the nutrients. As said, the technology greatly increased the nutrient penetration rate.

In addition to demonstrating the effectivity of this approach as compared to the standard spray method, the researchers also assessed the regulatory limitations associated with the spread of volatile particles.

”Our engineered liposomes are only stable within a short spraying range of up to 2 meters,” explained Prof. Schroeder. “If they travel in the air beyond that distance, they break down into safe materials (phospholipids). We hope that the success of this study will expand the research and development of similar agricultural products, to increase the yield and quality of food crops.”

This is an illustration of the work,

Each liposome (light blue bubble) was loaded with iron and magnesium particles. The liposomes sprayed on the leaves, penetrated and then spread throughout the various parts of the plant and released their load within the cells. Courtesy: Technion

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

Therapeutic nanoparticles penetrate leaves and deliver nutrients to agricultural crops by Avishai Karny, Assaf Zinger, Ashima Kajal, Janna Shainsky-Roitman, & Avi Schroeder. Scientific Reportsvolume 8, Article number: 7589 (2018) DOI: https://doi.org/10.1038/s41598-018-25197-y Published 17 May 2018

This paper is open access.

New semiconductor material from pigment produced by fungi?

Chlorociboria Aeruginascens fungus on a tree log. (Image: Oregon State University)

Apparently the pigment derived from the fungi you see in the above picture is used by visual artists and, perhaps soon, will be used by electronics manufacturers. From a June 5, 2018 news item on Nanowerk,

Researchers at Oregon State University are looking at a highly durable organic pigment, used by humans in artwork for hundreds of years, as a promising possibility as a semiconductor material.

Findings suggest it could become a sustainable, low-cost, easily fabricated alternative to silicon in electronic or optoelectronic applications where the high-performance capabilities of silicon aren’t required.

Optoelectronics is technology working with the combined use of light and electronics, such as solar cells, and the pigment being studied is xylindein.

A June 5, 2018 Oregon State University news release by Steve Lundeberg, which originated the news item, expands on the theme,

“Xylindein is pretty, but can it also be useful? How much can we squeeze out of it?” said Oregon State University [OSU] physicist Oksana Ostroverkhova. “It functions as an electronic material but not a great one, but there’s optimism we can make it better.”

Xylindien is secreted by two wood-eating fungi in the Chlorociboria genus. Any wood that’s infected by the fungi is stained a blue-green color, and artisans have prized xylindein-affected wood for centuries.

The pigment is so stable that decorative products made half a millennium ago still exhibit its distinctive hue. It holds up against prolonged exposure to heat, ultraviolet light and electrical stress.

“If we can learn the secret for why those fungi-produced pigments are so stable, we could solve a problem that exists with organic electronics,” Ostroverkhova said. “Also, many organic electronic materials are too expensive to produce, so we’re looking to do something inexpensively in an ecologically friendly way that’s good for the economy.”

With current fabrication techniques, xylindein tends to form non-uniform films with a porous, irregular, “rocky” structure.

“There’s a lot of performance variation,” she said. “You can tinker with it in the lab, but you can’t really make a technologically relevant device out of it on a large scale. But we found a way to make it more easily processed and to get a decent film quality.”

Ostroverkhova and collaborators in OSU’s colleges of Science and Forestry blended xylindein with a transparent, non-conductive polymer, poly(methyl methacrylate), abbreviated to PMMA and sometimes known as acrylic glass. They drop-cast solutions both of pristine xylindein and a xlyindein-PMMA blend onto electrodes on a glass substrate for testing.

They found the non-conducting polymer greatly improved the film structure without a detrimental effect on xylindein’s electrical properties. And the blended films actually showed better photosensitivity.

“Exactly why that happened, and its potential value in solar cells, is something we’ll be investigating in future research,” Ostroverkhova said. “We’ll also look into replacing the polymer with a natural product – something sustainable made from cellulose. We could grow the pigment from the cellulose and be able to make a device that’s all ready to go.

“Xylindein will never beat silicon, but for many applications, it doesn’t need to beat silicon,” she said. “It could work well for depositing onto large, flexible substrates, like for making wearable electronics.”

This research, whose findings were recently published in MRS Advances, represents the first use of a fungus-produced material in a thin-film electrical device.

“And there are a lot more of the materials,” Ostroverkhova said. “This is just first one we’ve explored. It could be the beginning of a whole new class of organic electronic materials.”

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

Fungi-Derived Pigments for Sustainable Organic (Opto)Electronics by Gregory Giesbers, Jonathan Van Schenck, Sarath Vega Gutierrez, Sara Robinson. MRS Advances https://doi.org/10.1557/adv.2018.446 Published online: 21 May 2018

This paper is behind a paywall.

Golden nanoglue

This starts out as a graphene story before taking an abrupt turn. From a June 5, 2018 news item on Nanowerk,

Graphene has undoubtedly been the most popular research subject of nanotechnology during recent years. Made of pure carbon, this material is in principle easy to manufacture: take ordinary graphite and peel one layer off with Scotch tape. The material thus obtained is two-dimensional, yielding unique properties, different from those in three-dimensional materials.

Graphene, however, lacks one important property, semiconductivity, which complicates its usage in electronics applications. Scientists have therefore started the quest of other two-dimensional materials with this desired property.

Molybdenum disulfide, MoS2 is among the most promising candidates. Like graphene, MoS2 consists of layers, interacting weakly with one another. In addition to being a semiconductor, the semiconducting properties of MoS2 change depending on the number of atomic layers.

A June 5, 2018 University of Oulu press release, which originated the news item,  gives more detail about the work,

For the one or few layer MoS2 to be useful in applications, one must be able to join it to other components. What is thus needed is such a metallic conductor that electric current can easily flow between the conductor and the semiconductor. In the case of MoS2, a promising conductor is provided by nickel, which also has other desired properties from the applications point of view.

However, an international collaboration, led by the Nano and molecular systems research unit at the University of Oulu has recently discovered that nanoparticles made of nickel do not attach to MoS2. One needs gold, which ‘glues’ the conductor and the component together. Says docent Wei Cao of NANOMO: “The synthesis is performed through a sonochemical method.” Sonochemistry is a method where chemical reactions are established using ultrasound. NANOMO scientist Xinying Shi adds: “The semiconductor and metal can be bridged either by the crystallized gold nanoparticles, or by the newly formed MoS2-Au-Ni ternary alloy.”

The nanojunction so established has a very small electrical resistivity. It also preserves the semiconducting and magnetic properties of MoS2. In addition, the new material has desirable properties beyond those of the original constituents. For example, it acts as a photocatalyst, which works much more efficiently than pure MoS2. Manufacturing the golden nanojunction is easy and cheap, which makes the new material attractive from the applications point of view.

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

Metallic Contact between MoS2 and Ni via Au Nanoglue by Xinying Shi, Sergei Posysaev, Marko Huttula, Vladimir Pankratov, Joanna Hoszowska, Jean‐Claude Dousse, Faisal Zeeshan, Yuran Niu, Alexei Zakharov, Taohai Li. Small Volume 14, Issue22 May 29, 2018 1704526 First published online: 24 April 2018 https://doi.org/10.1002/smll.201704526

This paper is behind a paywall.

There is a pretty illustration of the ‘golden nanojunctions’,

Golden nanoglue (Courtesy of the University of Oulu)

Using sound to transfer quantum information

It seems sound is becoming more prominent as a means of science data communication (data sonification) and in this upcoming case, data transfer. From a June 5, 2018 news item on ScienceDaily,

Quantum physics is on the brink of a technological breakthrough: new types of sensors, secure data transmission methods and maybe even computers could be made possible thanks to quantum technologies. However, the main obstacle here is finding the right way to couple and precisely control a sufficient number of quantum systems (for example, individual atoms).

A team of researchers from TU Wien and Harvard University has found a new way to transfer the necessary quantum information. They propose using tiny mechanical vibrations. The atoms are coupled with each other by ‘phonons’ — the smallest quantum mechanical units of vibrations or sound waves.

A June 5, 2018 Technical University of Vienna (TU Wien) press release, which originated the news item, explains the work in greater detail,

“We are testing tiny diamonds with built-in silicon atoms – these quantum systems are particularly promising,” says Professor Peter Rabl from TU Wien. “Normally, diamonds are made exclusively of carbon, but adding silicon atoms in certain places creates defects in the crystal lattice where quantum information can be stored.” These microscopic flaws in the crystal lattice can be used like a tiny switch that can be switched between a state of higher energy and a state of lower energy using microwaves.

Together with a team from Harvard University, Peter Rabl’s research group has developed a new idea to achieve the targeted coupling of these quantum memories within the diamond. One by one they can be built into a tiny diamond rod measuring only a few micrometres in length, like individual pearls on a necklace. Just like a tuning fork, this rod can then be made to vibrate – however, these vibrations are so small that they can only be described using quantum theory. It is through these vibrations that the silicon atoms can form a quantum-mechanical link to each other.

“Light is made from photons, the quantum of light. In the same way, mechanical vibrations or sound waves can also be described in a quantum-mechanical manner. They are comprised of phonons – the smallest possible units of mechanical vibration,” explains Peter Rabl. As the research team has now been able to show using simulation calculations, any number of these quantum memories can be linked together in the diamond rod thanks to these phonons. The individual silicon atoms are “switched on and off” using microwaves. During this process, they emit or absorb phonons. This creates a quantum entanglement of different silicon defects, thus allowing quantum information to be transferred.

The road to a scalable quantum network
Until now it was not clear whether something like this was even possible: “Usually you would expect the phonons to be absorbed somewhere, or to come into contact with the environment and thus lose their quantum mechanical properties,” says Peter Rabl. “Phonons are the enemy of quantum information, so to speak. But with our calculations, we were able to show that, when controlled appropriately using microwaves, the phonons are in fact useable for technical applications.”

The main advantage of this new technology lies in its scalability: “There are many ideas for quantum systems that, in principle, can be used for technological applications. The biggest problem is that it is very difficult to connect enough of them to be able to carry out complicated computing operations,” says Peter Rabl. The new strategy of using phonons for this purpose could pave the way to a scalable quantum technology.

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

Phonon Networks with Silicon-Vacancy Centers in Diamond Waveguides by M.-A. Lemonde, S. Meesala, A. Sipahigil, M. J. A. Schuetz, M. D. Lukin, M. Loncar, and P. Rabl. Phys. Rev. Lett. 120 (21), 213603 DOI:https://doi.org/10.1103/PhysRevLett.120.213603 Published 25 May 2018

This paper is behind a paywall.

Cryptology exhibit and special breakfast celebrating Canadian astronaut David Saint-Jacques’ Dec. 3, 2018 launch in Ontario (Canada)

I wish I was near either Ottawa or Kingston in December as there are a couple of very interesting events, assuming you have an interest in cryptology and/or space travel.

Cipher/Decipher

This show has been on tour in Ontario and, until Dec. 2, 2018, it will be at the Canada Science and Technology Museum before moving to Kingston (from the Canada Science and Technology Museum’s exhibitions page),

Cipher | Decipher

Pssst…want to know a secret?

One way to safely share secret information is through encryption — which means converting your message into something only the intended recipient can understand. For as long as we’ve had secret information, individuals and organizations have encrypted and analyzed encrypted communications. One way people encrypt their secrets is through ciphers that replace the original message with other letters, numbers, words, or symbols. From schoolyard gossip to military plans, ciphers keep secrets out of the wrong hands.

Cipher | Decipher is an interactive, new exhibition exploring the past and present of communications cryptology — what it is, how it works, and how it affects our lives. See an authentic Enigma cipher machine, or try your hand at logic puzzles and games to see if you have what it takes to work in the field of cryptology!

Developed by the Canada Science and Technology Museum, in partnership with the Communications Security Establishment, this 750 sq. ft. travelling exhibition is already on the move!

Mark your calendar to see Cipher | Decipher at the following locations:

  • Library and Archives Canada: October 5 to October 31, 2018
  • Canada Science and Technology Museum: November 6 to December 2, 2018
  • Military Communications and Electronics Museum, Kingston: December 7, 2018 to March 31, 2019

Blast-off!

This information came in a November 27, 2018 special announcement (received via email) from Ingenium (formerly Canada Science and Technology Museums Corporation and not to be confused with the Canada Science and Technology Museum),

Join the Canada Aviation and Space Museum for a special breakfast at the museum, as we witness the historic launch of Canadian astronaut David Saint-Jacques!

Start your day with a breakfast and a big cup of “rocket fuel” (a.k.a. coffee) as we watch the launch of this important space mission.

You’ll hear from Jesse Rogerson, the museum’s Science Advisor, and Iain Christie,

Executive Vice President of the Aerospace Industries Association of Canada about the intricacies of space travel. Canadian astronauts Bob Thirsk and Jenni Sidey-Gibbons will also join the conversation via livestream!

Take a selfie with our cut-out image of David Saint-Jacques, while the kids work on fun space-themed crafts. David Saint-Jacques themed merchandise will be 10% off during the event. Each purchase of a breakfast ticket/group of tickets will receive one FREE family pass, to visit the museum in 2019.

December 3, 2018
6 a.m. – 8:30 a.m.
Tickets: $16 (+ taxes)
Parking fees are additional.

Buy Tickets!

3… 2… 1… liftoff!

Enjoy!

First CRISPR gene-edited babies? Ethics and the science story

Scientists, He Jiankui and Michael Deem, may have created the first human babies born after being subjected to CRISPR (clustered regularly interspaced short palindromic repeats) gene editing.  At this point, no one is entirely certain that these babies  as described actually exist since the information was made public in a rather unusual (for scientists) fashion.

The news broke on Sunday, November 25, 2018 through a number of media outlets none of which included journals associated with gene editing or high impact journals such as Cell, Nature, or Science.The news broke in MIT Technology Review and in Associated Press. Plus, this all happened just before the Second International Summit on Human Genome Editing (Nov. 27 – 29, 2018) in Hong Kong. He Jiankui was scheduled to speak today, Nov. 27, 2018.

Predictably, this news has caused quite a tizzy.

Breaking news

Antonio Regalado broke the news in a November 25, 2018  article for MIT [Massachusetts Institute of Technology] Technology Review (Note: Links have been removed),

According to Chinese medical documents posted online this month (here and here), a team at the Southern University of Science and Technology, in Shenzhen, has been recruiting couples in an effort to create the first gene-edited babies. They planned to eliminate a gene called CCR5 in hopes of rendering the offspring resistant to HIV, smallpox, and cholera.

The clinical trial documents describe a study in which CRISPR is employed to modify human embryos before they are transferred into women’s uteruses.

The scientist behind the effort, He Jiankui, did not reply to a list of questions about whether the undertaking had produced a live birth. Reached by telephone, he declined to comment.

However, data submitted as part of the trial listing shows that genetic tests have been carried out on fetuses as late as 24 weeks, or six months. It’s not known if those pregnancies were terminated, carried to term, or are ongoing.

Apparently He changed his mind because Marilynn Marchione in a November 26, 2018 article for the Associated Press confirms the news,

A Chinese researcher claims that he helped make the world’s first genetically edited babies — twin girls born this month whose DNA he said he altered with a powerful new tool capable of rewriting the very blueprint of life.

If true, it would be a profound leap of science and ethics.

A U.S. scientist [Dr. Michael Deem] said he took part in the work in China, but this kind of gene editing is banned in the United States because the DNA changes can pass to future generations and it risks harming other genes.

Many mainstream scientists think it’s too unsafe to try, and some denounced the Chinese report as human experimentation.

There is no independent confirmation of He’s claim, and it has not been published in a journal, where it would be vetted by other experts. He revealed it Monday [November 26, 2018] in Hong Kong to one of the organizers of an international conference on gene editing that is set to begin Tuesday [November 27, 2018], and earlier in exclusive interviews with The Associated Press.

“I feel a strong responsibility that it’s not just to make a first, but also make it an example,” He told the AP. “Society will decide what to do next” in terms of allowing or forbidding such science.

Some scientists were astounded to hear of the claim and strongly condemned it.

It’s “unconscionable … an experiment on human beings that is not morally or ethically defensible,” said Dr. Kiran Musunuru, a University of Pennsylvania gene editing expert and editor of a genetics journal.

“This is far too premature,” said Dr. Eric Topol, who heads the Scripps Research Translational Institute in California. “We’re dealing with the operating instructions of a human being. It’s a big deal.”

However, one famed geneticist, Harvard University’s George Church, defended attempting gene editing for HIV, which he called “a major and growing public health threat.”

“I think this is justifiable,” Church said of that goal.

h/t Cale Guthrie Weissman’s Nov. 26, 2018 article for Fast Company.

Diving into more detail

Ed Yong in a November 26, 2018 article for The Atlantic provides more details about the claims (Note: Links have been removed),

… “Two beautiful little Chinese girls, Lulu and Nana, came crying into the world as healthy as any other babies a few weeks ago,” He said in the first of five videos, posted yesterday {Nov. 25, 2018] to YouTube [link provided at the end of this section of the post]. “The girls are home now with their mom, Grace, and dad, Mark.” The claim has yet to be formally verified, but if true, it represents a landmark in the continuing ethical and scientific debate around gene editing.

Late last year, He reportedly enrolled seven couples in a clinical trial, and used their eggs and sperm to create embryos through in vitro fertilization. His team then used CRISPR to deactivate a single gene called CCR5 in the embryos, six of which they then implanted into mothers. CCR5 is a protein that the HIV virus uses to gain entry into human cells; by deactivating it, the team could theoretically reduce the risk of infection. Indeed, the fathers in all eight couples were HIV-positive.

Whether the experiment was successful or not, it’s intensely controversial. Scientists have already begun using CRISPR and other gene-editing technologies to alter human cells, in attempts to treat cancers, genetic disorders, and more. But in these cases, the affected cells stay within a person’s body. Editing an embryo [it’s often called, germline editing] is very different: It changes every cell in the body of the resulting person, including the sperm or eggs that would pass those changes to future generations. Such work is banned in many European countries, and prohibited in the United States. “I understand my work will be controversial, but I believe families need this technology and I’m willing to take the criticism for them,” He said.

“Was this a reasonable thing to do? I would say emphatically no,” says Paula Cannon of the University of Southern California. She and others have worked on gene editing, and particularly on trials that knock out CCR5 as a way to treat HIV. But those were attempts to treat people who were definitively sick and had run out of other options. That wasn’t the case with Nana and Lulu.

“The idea that being born HIV-susceptible, which is what the vast majority of humans are, is somehow a disease state that requires the extraordinary intervention of gene editing blows my mind,” says Cannon. “I feel like he’s appropriating this potentially valuable therapy as a shortcut to doing something in the sphere of gene editing. He’s either very naive or very cynical.”

“I want someone to make sure that it has happened,” says Hank Greely, an ethicist at Stanford University. If it hasn’t, that “would be a pretty bald-faced fraud,” but such deceptions have happened in the past. “If it is true, I’m disappointed. It’s reckless on safety grounds, and imprudent and stupid on social grounds.” He notes that a landmark summit in 2015 (which included Chinese researchers) and a subsequent major report from the National Academies of Science, Engineering, and Medicine both argued that “public participation should precede any heritable germ-line editing.” That is: Society needs to work out how it feels about making gene-edited babies before any babies are edited. Absent that consensus, He’s work is “waving a red flag in front of a bull,” says Greely. “It provokes not just the regular bio-Luddites, but also reasonable people who just wanted to talk it out.”

Societally, the creation of CRISPR-edited babies is a binary moment—a Rubicon that has been crossed. But scientifically, the devil is in the details, and most of those are still unknown.

CRISPR is still inefficient. [emphasis mine] The Chinese teams who first used it to edit human embryos only did so successfully in a small proportion of cases, and even then, they found worrying levels of “off-target mutations,” where they had erroneously cut parts of the genome outside their targeted gene. He, in his video, claimed that his team had thoroughly sequenced Nana and Lulu’s genomes and found no changes in genes other than CCR5.

That claim is impossible to verify in the absence of a peer-reviewed paper, or even published data of any kind. “The paper is where we see whether the CCR5 gene was properly edited, what effect it had at the cellular level, and whether [there were] any off-target effects,” said Eric Topol of the Scripps Research Institute. “It’s not just ‘it worked’ as a binary declaration.”

In the video, He said that using CRISPR for human enhancement, such as enhancing IQ or selecting eye color, “should be banned.” Speaking about Nana and Lulu’s parents, he said that they “don’t want a designer baby, just a child who won’t suffer from a disease that medicine can now prevent.”

But his rationale is questionable. Huang [Junjiu Huang of Sun Yat-sen University ], the first Chinese researcher to use CRISPR on human embryos, targeted the faulty gene behind an inherited disease called beta thalassemia. Mitalipov, likewise, tried to edit a gene called MYBPC3, whose faulty versions cause another inherited disease called hypertrophic cardiomyopathy (HCM). Such uses are still controversial, but they rank among the more acceptable applications for embryonic gene editing as ways of treating inherited disorders for which treatments are either difficult or nonexistent.

In contrast, He’s team disableda normal gene in an attempt to reduce the risk of a disease that neither child had—and one that can be controlled. There are already ways of preventing fathers from passing HIV to their children. There are antiviral drugs that prevent infections. There’s safe-sex education. “This is not a plague for which we have no tools,” says Cannon.

As Marilynn Marchione of the AP reports, early tests suggest that He’s editing was incomplete [emphasis mine], and at least one of the twins is a mosaic, where some cells have silenced copies of CCR5 and others do not. If that’s true, it’s unlikely that they would be significantly protected from HIV. And in any case, deactivating CCR5 doesn’t confer complete immunity, because some HIV strains can still enter cells via a different protein called CXCR4.

Nana and Lulu might have other vulnerabilities. …

It is also unclear if the participants in He’s trial were fully aware of what they were signing up for. [emphasis mine] The team’s informed-consent document describes their work as an “AIDS vaccine development project,” and while it describes CRISPR gene editing, it does so in heavily technical language. It doesn’t mention any of the risks of disabling CCR5, and while it does note the possibility of off-target effects, it also says that the “project team is not responsible for the risk.”

He owns two genetics companies, and his collaborator, Michael Deem of Rice University,  [emphasis mine] holds a small stake in, and sits on the advisory board of, both of them. The AP’s Marchione reports, “Both men are physics experts with no experience running human clinical trials.” [emphasis mine]

Yong’s article is well worth reading in its entirety. As for YouTube, here’s The He Lab’s webpage with relevant videos.

Reactions

Gina Kolata, Sui-Lee Wee, and Pam Belluck writing in a Nov. 26, 2018 article for the New York Times chronicle some of the response to He’s announcement,

It is highly unusual for a scientist to announce a groundbreaking development without at least providing data that academic peers can review. Dr. He said he had gotten permission to do the work from the ethics board of the hospital Shenzhen Harmonicare, but the hospital, in interviews with Chinese media, denied being involved. Cheng Zhen, the general manager of Shenzhen Harmonicare, has asked the police to investigate what they suspect are “fraudulent ethical review materials,” according to the Beijing News.

The university that Dr. He is attached to, the Southern University of Science and Technology, said Dr. He has been on no-pay leave since February and that the school of biology believed that his project “is a serious violation of academic ethics and academic norms,” according to the state-run Beijing News.

In a statement late on Monday, China’s national health commission said it has asked the health commission in southern Guangdong province to investigate Mr. He’s claims.

“I think that’s completely insane,” said Shoukhrat Mitalipov, director of the Center for Embryonic Cell and Gene Therapy at Oregon Health and Science University. Dr. Mitalipov broke new ground last year by using gene editing to successfully remove a dangerous mutation from human embryos in a laboratory dish. [I wrote a three-part series about CRISPR, which included what was then the latest US news, Mitalipov’s announcement, along with a roundup of previous work in China. Links are at the end of this section.’

Dr. Mitalipov said that unlike his own work, which focuses on editing out mutations that cause serious diseases that cannot be prevented any other way, Dr. He did not do anything medically necessary. There are other ways to prevent H.I.V. infection in newborns.

Just three months ago, at a conference in late August on genome engineering at Cold Spring Harbor Laboratory in New York, Dr. He presented work on editing the CCR₅ gene in the embryos of nine couples.

At the conference, whose organizers included Jennifer Doudna, one of the inventors of Crispr technology, Dr. He gave a careful talk about something that fellow attendees considered squarely within the realm of ethically approved research. But he did not mention that some of those embryos had been implanted in a woman and could result in genetically engineered babies.

“What we now know is that as he was talking, there was a woman in China carrying twins,” said Fyodor Urnov, deputy director of the Altius Institute for Biomedical Sciences and a visiting researcher at the Innovative Genomics Institute at the University of California. “He had the opportunity to say ‘Oh and by the way, I’m just going to come out and say it, people, there’s a woman carrying twins.’”

“I would never play poker against Dr. He,” Dr. Urnov quipped.

Richard Hynes, a cancer researcher at the Massachusetts Institute of Technology, who co-led an advisory group on human gene editing for the National Academy of Sciences and the National Academy of Medicine, said that group and a similar organization in Britain had determined that if human genes were to be edited, the procedure should only be done to address “serious unmet needs in medical treatment, it had to be well monitored, it had to be well followed up, full consent has to be in place.”

It is not clear why altering genes to make people resistant to H.I.V. is “a serious unmet need.” Men with H.I.V. do not infect embryos. …

Dr. He got his Ph.D., from Rice University, in physics and his postdoctoral training, at Stanford, was with Stephen Quake, a professor of bioengineering and applied physics who works on sequencing DNA, not editing it.

Experts said that using Crispr would actually be quite easy for someone like Dr. He.

After coming to Shenzhen in 2012, Dr. He, at age 28, established a DNA sequencing company, Direct Genomics, and listed Dr. Quake on its advisory board. But, in a telephone interview on Monday, Dr. Quake said he was never associated with the company.

Deem, the US scientist who worked in China with He is currently being investigated (from a Nov. 26, 2018 article by Andrew Joseph in STAT),

Rice University said Monday that it had opened a “full investigation” into the involvement of one of its faculty members in a study that purportedly resulted in the creation of the world’s first babies born with edited DNA.

Michael Deem, a bioengineering professor at Rice, told the Associated Press in a story published Sunday that he helped work on the research in China.

Deem told the AP that he was in China when participants in the study consented to join the research. Deem also said that he had “a small stake” in and is on the scientific advisory boards of He’s two companies.

Megan Molteni in a Nov. 27, 2018 article for Wired admits she and her colleagues at the magazine may have dismissed CRISPR concerns about designer babies prematurely while shedding more light on this  latest development (Note: Links have been removed),

We said “don’t freak out,” when scientists first used Crispr to edit DNA in non-viable human embryos. When they tried it in embryos that could theoretically produce babies, we said “don’t panic.” Many years and years of boring bench science remain before anyone could even think about putting it near a woman’s uterus. Well, we might have been wrong. Permission to push the panic button granted.

Late Sunday night, a Chinese researcher stunned the world by claiming to have created the first human babies, a set of twins, with Crispr-edited DNA….

What’s perhaps most strange is not that He ignored global recommendations on conducting responsible Crispr research in humans. He also ignored his own advice to the world—guidelines that were published within hours of his transgression becoming public.

On Monday, He and his colleagues at Southern University of Science and Technology, in Shenzhen, published a set of draft ethical principles “to frame, guide, and restrict clinical applications that communities around the world can share and localize based on religious beliefs, culture, and public-health challenges.” Those principles included transparency and only performing the procedure when the risks are outweighed by serious medical need.

The piece appeared in the The Crispr Journal, a young publication dedicated to Crispr research, commentary, and debate. Rodolphe Barrangou, the journal’s editor in chief, where the peer-reviewed perspective appeared, says that the article was one of two that it had published recently addressing the ethical concerns of human germline editing, the other by a bioethicist at the University of North Carolina. Both papers’ authors had requested that their writing come out ahead of a major gene editing summit taking place this week in Hong Kong. When half-rumors of He’s covert work reached Barrangou over the weekend, his team discussed pulling the paper, but ultimately decided that there was nothing too solid to discredit it, based on the information available at the time.

Now Barrangou and his team are rethinking that decision. For one thing, He did not disclose any conflicts of interest, which is standard practice among respectable journals. It’s since become clear that not only is He at the helm of several genetics companies in China, He was actively pursuing controversial human research long before writing up a scientific and moral code to guide it.“We’re currently assessing whether the omission was a matter of ill-management or ill-intent,” says Barrangou, who added that the journal is now conducting an audit to see if a retraction might be warranted. …

“There are all sorts of questions these issues raise, but the most fundamental is the risk-benefit ratio for the babies who are going to be born,” says Hank Greely, an ethicist at Stanford University. “And the risk-benefit ratio on this stinks. Any institutional review board that approved it should be disbanded if not jailed.”

Reporting by Stat indicates that He may have just gotten in over his head and tried to cram a self-guided ethics education into a few short months. The young scientist—records indicate He is just 34—has a background in biophysics, with stints studying in the US at Rice University and in bioengineer Stephen Quake’s lab at Stanford. His resume doesn’t read like someone steeped deeply in the nuances and ethics of human research. Barrangou says that came across in the many rounds of edits He’s framework went through.

… China’s central government in Beijing has yet to come down one way or another. Condemnation would make He a rogue and a scientific outcast. Anything else opens the door for a Crispr IVF cottage industry to emerge in China and potentially elsewhere. “It’s hard to imagine this was the only group in the world doing this,” says Paul Knoepfler, a stem cell researcher at UC Davis who wrote a book on the future of designer babies called GMO Sapiens. “Some might say this broke the ice. Will others forge ahead and go public with their results or stop what they’re doing and see how this plays out?”

Here’s some of the very latest information with the researcher attempting to explain himself.

What does He have to say?

After He’s appearance at the Second International Summit on Human Genome Editing today, Nov. 27, 2018, David Cyranoski produced this article for Nature,

He Jiankui, the Chinese scientist who claims to have helped produce the first people born with edited genomes — twin girls — appeared today at a gene-editing summit in Hong Kong to explain his experiment. He gave his talk amid threats of legal action and mounting questions, from the scientific community and beyond, about the ethics of his work and the way in which he released the results.

He had never before presented his work publicly outside of a handful of videos he posted on YouTube. Scientists welcomed the fact that he appeared at all — but his talk left many hungry for more answers, and still not completely certain that He has achieved what he claims.

“There’s no reason not to believe him,” says Robin Lovell-Badge, a developmental biologist at the Francis Crick Institute in London. “I’m just not completely convinced.”

Lovell-Badge, like others at the conference, says that an independent body should confirm the test results by performing an in-depth comparison of the parents’ and childrens’ genes.

Many scientists faulted He for a lack of transparency and the seemingly cavalier nature in which he embarked on such a landmark, and potentially risky, project.

“I’m happy he came but I was really horrified and stunned when he described the process he used,” says Jennifer Doudna, a biochemist at the University of California, Berkeley and a pioneer of the CRISPR/Cas-9 gene-editing technique that He used. “It was so inappropriate on so many levels.”

He seemed shaky approaching the stage and nervous during the talk. “I think he was scared,” says Matthew Porteus, who researches genome-editing at Stanford University in California and co-hosted a question-and-answer session with He after his presentation. Porteus attributes this either to the legal pressures that He faces or the mounting criticism from the scientists and media he was about to address.

He’s talk leaves a host of other questions unanswered, including whether the prospective parents were properly informed of the risks; why He selected CCR5 when there are other, proven ways to prevent HIV; why he chose to do the experiment with couples in which the fathers have HIV, rather than mothers who have a higher chance of passing the virus on to their children; and whether the risks of knocking out CCR5 — a gene normally present in people, which could have necessary but still unknown functions — outweighed the benefits in this case.

In the discussion following He’s talk, one scientist asked why He proceeded with the experiments despite the clear consensus among scientists worldwide that such research shouldn’t be done. He didn’t answer the question.

He’s attempts to justify his actions mainly fell flat. In response to questions about why the science community had not been informed of the experiments before the first women were impregnated, he cited presentations that he gave last year at meetings at the University of California, Berkeley, and at the Cold Spring Harbor Laboratory in New York. But Doudna, who organized the Berkeley meeting, says He did not present anything that showed he was ready to experiment in people. She called his defence “disingenuous at best”.

He also said he discussed the human experiment with unnamed scientists in the United States. But Porteus says that’s not enough for such an extraordinary experiment: “You need feedback not from your two closest friends but from the whole community.” …

Pressure was mounting on He ahead of the presentation. On 27 November, the Chinese national health commission ordered the Guangdong health commission, in the province where He’s university is located, to investigate.

On the same day, the Chinese Academy of Sciences issued a statement condemning his work, and the Genetics Society of China and the Chinese Society for Stem Cell Research jointly issued a statement saying the experiment “violates internationally accepted ethical principles regulating human experimentation and human rights law”.

The hospital cited in China’s clinical-trial registry as the that gave ethical approval for He’s work posted a press release on 27 November saying it did not give any approval. It questioned the signatures on the approval form and said that the hospital’s medical-ethics committee never held a meeting related to He’s research. The hospital, which itself is under investigation by the Shenzhen health authorities following He’s revelations, wrote: “The Company does not condone the means of the Claimed Project, and has reservations as to the accuracy, reliability and truthfulness of its contents and results.”

He has not yet responded to requests for comment on these statements and investigations, nor on why the hospital was listed in the registry and the claim of apparent forged signatures.

Alice Park’s Nov. 26, 2018 article for Time magazine includes an embedded video of He’s Nov. 27, 2018 presentation at the summit meeting.

What about the politics?

Mara Hvistendahl’s Nov. 27, 2018 article about this research for Slate.com poses some geopolitical questions (Note: Links have been removed),

The informed consent agreement for He Jiankui’s experiment describes it as an “AIDS vaccine development project” and used highly technical language to describe the procedure that patients would undergo. If the reality for some Chinese patients is that such agreements are glossed over, densely written, or never read, the reality for some researchers working in the country is that the appeal of cutting-edge trials is too great to resist. It is not just Chinese scientists who can be blinded by the lure of quick breakthroughs. Several of the most notable breaches of informed consent on the mainland have involved Western researchers or co-authors. … When people say that the usual rules don’t apply in China, they are really referring to authoritarian science, not some alternative communitarian ethics.

For the many scientists in China who adhere to recognized international standards, the incident comes as a disgrace. He Jiankui now faces an ethics investigation from provincial health authorities, and his institution, Southern University of Science and Technology, was quick to issue a statement noting that He was on unpaid leave. …

It would seem that US scientists wanting to avoid pesky ethics requirements in the US have found that going to China could be the answer to their problems. I gather it’s not just big business that prefers deregulated environments.

Guillaume Levrier’s  (he’ studying for a PhD at the Universté Sorbonne Paris Cité) November 16, 2018 essay for The Conversation sheds some light on political will and its impact on science (Note: Links have been removed),

… China has entered a “genome editing” race among great scientific nations and its progress didn’t come out of nowhere. China has invested heavily in the natural-sciences sector over the past 20 years. The Ninth Five-Year Plan (1996-2001) mentioned the crucial importance of biotechnologies. The current Thirteenth Five-Year Plan is even more explicit. It contains a section dedicated to “developing efficient and advanced biotechnologies” and lists key sectors such as “genome-editing technologies” intended to “put China at the bleeding edge of biotechnology innovation and become the leader in the international competition in this sector”.

Chinese embryo research is regulated by a legal framework, the “technical norms on human-assisted reproductive technologies”, published by the Science and Health Ministries. The guidelines theoretically forbid using sperm or eggs whose genome have been manipulated for procreative purposes. However, it’s hard to know how much value is actually placed on this rule in practice, especially in China’s intricate institutional and political context.

In theory, three major actors have authority on biomedical research in China: the Science and Technology Ministry, the Health Ministry, and the Chinese Food and Drug Administration. In reality, other agents also play a significant role. Local governments interpret and enforce the ministries’ “recommendations”, and their own interpretations can lead to significant variations in what researchers can and cannot do on the ground. The Chinese National Academy of Medicine is also a powerful institution that has its own network of hospitals, universities and laboratories.

Another prime actor is involved: the health section of the People’s Liberation Army (PLA), which has its own biomedical faculties, hospitals and research labs. The PLA makes its own interpretations of the recommendations and has proven its ability to work with the private sector on gene editing projects. …

One other thing from Levrier’s essay,

… And the media timing is just a bit too perfect, …

Do read the essay; there’s a twist at the end.

Final thoughts and some links

If I read this material rightly, there are suspicions there may be more of this work being done in China and elsewhere. In short, we likely don’t have the whole story.

As for the ethical issues, this is a discussion among experts only, so far. The great unwashed (thee and me) are being left at the wayside. Sure, we’ll be invited to public consultations, one day,  after the big decisions have been made.

Anyone who’s read up on the history of science will tell you this kind of breach is very common at the beginning. Richard Holmes’  2008 book, ‘The Age of Wonder: How the Romantic Generation Discovered the Beauty and Terror of Science’ recounts stories of early scientists (European science) who did crazy things. Some died, some shortened their life spans; and, some irreversibly damaged their health.  They also experimented on other people. Informed consent had not yet been dreamed up.

In fact, I remember reading somewhere that the largest human clinical trial in history was held in Canada. The small pox vaccine was highly contested in the US but the Canadian government thought it was a good idea so they offered US scientists the option of coming here to vaccinate Canadian babies. This was in the 1950s and the vaccine seems to have been administered almost universally. That was a lot of Canadian babies. Thankfully, it seems to have worked out but it does seem mind-boggling today.

For all the indignation and shock we’re seeing, this is not the first time nor will it be the last time someone steps over a line in order to conduct scientific research. And, that is the eternal problem.

Meanwhile I think some of the real action regarding CRISPR and germline editing is taking place in the field (pun!) of agriculture:

My Nov. 27, 2018 posting titled: ‘Designer groundcherries by CRISPR (clustered regularly interspaced short palindromic repeats)‘ and a more disturbing Nov. 27, 2018 post titled: ‘Agriculture and gene editing … shades of the AquAdvantage salmon‘. That second posting features a company which is trying to sell its gene-editing services to farmers who would like cows that  never grow horns and pigs that never reach puberty.

Then there’s this ,

The Genetic Revolution‘, a documentary that offers relatively up-to-date information about gene editing, which was broadcast on Nov. 11, 2018 as part of The Nature of Things series on CBC (Canadian Broadcasting Corporation).

My July 17, 2018 posting about research suggesting that scientists hadn’t done enough research on possible effects of CRISPR editing titled: ‘The CRISPR ((clustered regularly interspaced short palindromic repeats)-CAS9 gene-editing technique may cause new genetic damage kerfuffle’.

My 2017 three-part series on CRISPR and germline editing:

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

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

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

There you have it.

Added on November 30, 2018: David Cyanowski has written one final article (Nov. 30, 2018 for Nature) about He and the Second International Summit on Human Genome Editing. He did not make his second scheduled appearance at the summit, returning to China before the summit concluded. He was rebuked in a statement produced by the Summit’s organizing committee at the end of the three-day meeting. The situation with regard to his professional status in China is ambiguous. Cyanowski ends his piece with the information that the third summit will take place in London (likely in the UK) in 2021. I encourage you to read Cyanowski’s Nov. 30, 2018 article in its entirety; it’s not long.

Added on Dec. 3, 2018: The story continues. Ed Yong has written a summary of the issues to date in a Dec. 3, 2018 article for The Atlantic (even if you know the story ift’s eyeopening to see all the parts put together.

J. Benjamin Hurlbut, Associate Professor of Life Sciences at Arizona State University (ASU) and Jason Scott Robert, Director of the Lincoln Center for Applied Ethics at Arizona State University have written a provocative (and true) Dec. 3, 2018 essay titled, CRISPR babies raise an uncomfortable reality – abiding by scientific standards doesn’t guarantee ethical research, for The Conversation. h/t phys.org