Tag Archives: Chinese Academy of Sciences

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

Multi-level thinking in science—the art of seeing systems

I’ve quickly read Michael Edgeworth McIntyre’s paper on multi-level thinking and find it provides fascinating insight and some good writing style (I’ve provided a few excerpts from the paper further down in the posting).

Here’s more about the paper from an Aug. 17, 2017 Institute of Atmospheric Physics, Chinese Academy of Sciences press release on EurekAlert,

An unusual paper “On multi-level thinking and scientific understanding” appears in the October issue of Advances in Atmospheric Sciences. The author is Professor Michael Edgeworth McIntyre from University of Cambridge, whose work in atmospheric dynamics is well known. He has also had longstanding interests in astrophysics, music, perception psychology, and biological evolution.

The paper touches on a range of deep questions within and outside the atmospheric sciences. They include insights into the nature of science itself, and of scientific understanding — what it means to understand a scientific problem in depth — and into the communication skills necessary to convey that understanding and to mediate collaboration across specialist disciplines.

The paper appears in a Special Issue arising from last year’s Symposium held in Nanjing to commemorate the life of Professor Duzheng YE, who was well known as a national and international scientific leader and for his own wide range of interests, within and outside the atmospheric sciences. The symposium was organized by the Institute of Atmospheric Physics (IAP), Chinese Academy of Sciences, where Prof. YE had worked nearly 70 years before he passed away. Upon the invitation of Prof. Jiang ZHU, the Director General of IAP, also the Editor-in-Chief of Advances in Atmospheric Sciences (AAS), Prof. McIntyre agreed to contribute a review paper to an AAS special issue commemorating the centenary of Duzheng YE’s birth. Prof. YE was also the founding Editor-in-Chief of this journal.

One of Professor McIntyre’s themes is that we all have unconscious mathematics, including Euclidean geometry and the calculus of variations. This is easy to demonstrate and is key to understanding not only how science works but also, for instance, how music works. Indeed, it reveals some of the deepest connections between music and mathematics, going beyond the usual remarks about number-patterns. All this revolves around the biological significance of what Professor McIntyre calls the “organic-change principle”.

Further themes include the scientific value of looking at a problem from more than one viewpoint, and the need to use more than one level of description. Many scientific and philosophical controversies stem from confusing one level of description with another, for instance applying arguments to one level that belong on another. This confusion can be especially troublesome when it comes to questions about human biology and human nature, and about what Professor YE called multi-level “orderly human activities”.

Related to all these points are the contrasting modes of perception and understanding offered by the brain’s left and right hemispheres. Our knowledge of their functioning has progressed far beyond the narrow clichés of popular culture, thanks to recent work in the neurosciences. The two hemispheres automatically give us different levels of description, and complementary views of a problem. Good science takes advantage of this. When the two hemispheres cooperate, with each playing to its own strengths, our problem-solving is at its most powerful.

The paper ends with three examples of unconscious assumptions that have impeded scientific progress in the past. Two of them are taken from Professor McIntyre’s main areas of research. A third is from biology.

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

On multi-level thinking and scientific understanding by Michael Edgeworth McIntyre. Advances in Atmospheric Sciences October 2017, Volume 34, Issue 10, pp 1150–1158 DOI: https://doi.org/10.1007/s00376-017-6283-3

This paper is open access.

To give you a sense of his writing and imagination, I’ve excerpted a few paragraphs from p. 1153 but first you need to see this .gif (he provides a number of ways to watch the .gif in his text but I think it’s easier to watch the copy of the one he has on his website),

Now for the excerpt,

Here is an example to show what I mean. It is a classic in experimental psychology, from the work of Professor Gunnar JOHANSSON in the 1970s. …

As soon as the twelve dots start moving, everyone with normal vision sees a person walking. This immediately illustrates several things. First, it illustrates that we all make unconscious assumptions. Here, we unconsciously assume a particular kind of three-dimensional motion. In this case the unconscious assumption is completely involuntary. We cannot help seeing a person walking, despite knowing that it is only twelve moving dots.

The animation also shows that we have unconscious mathematics, Euclidean geometry in this case. In order to generate the percept of a person walking, your brain has to fit a mathematical model to the incoming visual data, in this case a mathematical model based on Euclidean geometry. (And the model-fitting process is an active, and highly complex, predictive process most of which is inaccessible to conscious introspection.)

This brings me to the most central point in our discussion. Science does essentially the same thing. It fits models to data. So science is, in the most fundamental possible sense, an extension of ordinary perception. That is a simple way of saying what was said many decades ago by great thinkers such as Professor Sir Karl POPPER….

I love that phase “unconscious mathematics” for the way it includes even those of us who would never dream of thinking we had any kind of mathematics. I encourage you to read his paper in its entirety, which does include a little technical language in a few spots but the overall thesis is clear and easily understood.

China and the world’s largest multifunctional research platform for nanotechnology

Weirdly, I got this news about China in a March 28 (?), 2017 news item from the Nigeria News Agency,

Chinese scientists are building the world’s largest multifunctional research platform for nano-science and nano-technology that could help develop more powerful computers and more intelligent robots.

The Vacuum Interconnected Nano-X Research Facility in Suzhou, Jiangsu Province, integrates the state-of-art capabilities of material growth, device fabrication and testing in one ultra-high vacuum environment, said Ding Sunan, deputy director of the project.

“We are exploring a new technology route of nano-scale devices production on the platform, which simulates the ultra-high vacuum environment of space,” said Ding, a researcher at the Suzhou Institute of Nano-Tech and Nano-Bionics under the Chinese Academy of Sciences.

Nano-X is designed as a complete system for materials growth, device fabrication and testing. All samples can be transferred accurately, quickly and smoothly among all tools in an ultra-high vacuum environment.

The facility can prevent surface contamination from the air, keeping a material’s intrinsic properties unchanged and realizing quantum manipulation and control, said Ding.

Experts say it will help make breakthroughs in common and critical problems in materials science and device technology, and develop new manufacturing technologies of nano-materials and core devices in the fields of energy and information.

Nano-X is expected to be incorporated into China’s national research infrastructure system, and become a world-class open platform for research and development in nano-science and nano-technology, providing advanced technical support for the national strategy of high technologies.

I’ve come across ‘Suzhou’ and nanotechnology in China before but first, here are a few more details about Nano-X in a March 29, 2017 news item by PTI on the bgr.in (India) website,

Nano-X has received initial funding of 320 million Yuan (about $46.5 million) and will eventually have a budget of 1.5 billion Yuan, state-run Xinhua news agency reported. Construction of the first stage began in 2014 and is expected to be completed in 2018. It comprises 100-metre-long ultra-high vacuum pipelines connecting 30 pieces of equipment. Ultimately the facility will have ultra-high vacuum pipelines of about 500 metres, connecting more than 100 large pieces of equipment, Ding said.

I gather Nano-X is part of the Suzhou Industrial Park’s Nanopolis. I’m somewhat confused about Nanopolis since I wrote in a Sept.. 26, 2014 posting that it hadn’t yet opened officially but the Nanopolis Background webpage suggests is been open since 2013,

On the journey of starting a new undertaking led by the industry transformation and upgrading campaign, Suzhou Industrial Park has chosen the nanotech application industry as the strategic emerging industry to lead the campaign, as the first one in China that has taken this initiative. 

officially [sic] put into use  in 2013 as a key component of the nanotech advancement strategy, and has developed into the main battlefield of Suzhou Industrial Park for nanotechnology applications.

In the concept of “industry ecosystem” for nanotech applications, Nanopolis Suzhou focuses on new sectors, pools creative resources and invents new models to build a high-end, leading platform that’s innovation and development friendly so as to promote the transformation and upgrading of the regional industries.

In any event, Nanopolis now bills itself as (from the Nanopolis Overview webpage),

… the world’s largest hub of nanotech innovation and commercialization [emphasis mine] with a floorage of 100 acres and a planned construction area of 1.5 million m2. Besides,it’s also the China International Nanotech Innovation Cluster and the core area of the National Nano Hi-tech Industry Base.

I imagine there will be many openings for buildings and other initiatives.

Inspiration from the sea for titanium implants (mussels) and adhesive panels for flexible sensors (octopuses/octopi/octopodes)

I have two sea-inspired news bits both of which concern adhesion.

Mussels and titanium implants

A July 8, 2016 news item on ScienceDaily features some mussel-inspired research from Japan into how to make better titanium implants,

Titanium is used medically in applications such as artificial joints and dental implants. While it is strong and is not harmful to tissues, the metal lacks some of the beneficial biological properties of natural tissues such as bones and natural teeth. Now, based on insights from mussels–which are able to attach themselves very tightly to even metallic surfaces due to special proteins found in their byssal threads–scientists from RIKEN have successfully attached a biologically active molecule to a titanium surface, paving the way for implants that can be more biologically beneficial.

A July 11, 2016 RIKEN press release (also on EurekAlert but dated July 8, 2016), which originated the news item, provides more information,

The work began from earlier discoveries that mussels can attach to smooth surfaces so effectively thanks to a protein, L-DOPA, which is known to be able to bind very strongly to smooth surfaces such as rocks, ceramics, or metals (…). Interestingly, the same protein functions in humans as a precursor to dopamine, and is used as a treatment for Parkinson’s disease.

According to Chen Zhang of the RIKEN Nano Medical Engineering Laboratory, the first author of the paper published in Angewandte Chemie, “We thought it would be interesting to try to use various techniques to attach a biologically active protein—in our case we chose insulin-like growth factor-1, a promoter of cell proliferation—to a titanium surface like those used in implants” (…).

Using a combination of recombinant DNA technology and treatment with tyrosinase, they were able to create a hybrid protein that contained active parts of both the growth factor and L-DOPA. Tests showed that the proteins were able to fold normally, and further experiments in cell cultures demonstrated that the IGF-1 was still functioning normally. Thanks to the incorporation of the L-DOPA, the team was able to confirm that the proteins bound strongly to the titanium surface, and remained attached even when the metal was washed with phosphate-buffered saline, a water-based solution. Zhang says, “This is similar to the powerful properties of mussel adhesive, which can remain fixed to metallic materials even underwater.”

According to Yoshihiro Ito, Team Leader of the Emergent Bioengineering Research Team of the RIKEN Center for Emergent Matter Science, “We are very excited by this finding, because the modification process is a universal one that could be used with other proteins. It could allow us to prepare new cell-growth enhancing materials, with potential applications in cell culture systems and regenerative medicine. And it is particularly interesting that this is an example of biomimetics, where nature can teach us new ways to do things. The mussel has given us insights that could be used to allow us to live healthier lives.”

The work was done by RIKEN researchers in collaboration with Professor Peibiao Zhang of the Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, and Professor Yi Wang of the School of Pharmaceutical Sciences, Jilin University. The work was partially supported by the Japan Society for the Promotion of Science KAKENHI (Grant Number 15H01810 and 22220009), CAS-JSPS joint fund (GJHZ1519), and RIKEN MOST joint project.

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

A Bioorthogonal Approach for the Preparation of a Titanium-Binding Insulin-like Growth-Factor-1 Derivative by using Tyrosinase by Chen Zhang, Hideyuki Miyatake, Yu Wang, Takehiko Inaba, Yi Wang, Peibiao Zhang, and Prof. Yoshihiro Ito. Angewandte Chemie International Edition DOI: 10.1002/anie.201603155 Version of Record online: 6 JUL 2016

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

Octopuses/octopi/octopodes and adhesive panels

Before launching into the science part of this news bit, here’s some grammar (from the Octopus Wikipedia entry; Note: Links have been removed),

The standard pluralized form of “octopus” in the English language is “octopuses” /ˈɒktəpʊsɪz/,[10] although the Ancient Greek plural “octopodes” /ɒkˈtɒpədiːz/, has also been used historically.[9] The alternative plural “octopi” — which misguidedly assumes it is a Latin “-us”-word — is considered grammatically incorrect.[11][12][13][14] It is nevertheless used enough to make it notable, and was formally acknowledged by the descriptivist Merriam-Webster 11th Collegiate Dictionary and Webster’s New World College Dictionary. The Oxford English Dictionary (2008 Draft Revision)[15] lists “octopuses”, “octopi”, and “octopodes”, in that order, labelling “octopodes” as rare and noting that “octopi” derives from the apprehension that octōpus comes from Latin.[16] In contrast, New Oxford American Dictionary (3rd Edition 2010) lists “octopuses” as the only acceptable pluralization, with a usage note indicating “octopodes” as being still occasionally used but “octopi” as being incorrect.[17]

Now the news. A July 12, 2016 news item on Nanowerk highlights some research into adhesives and octopuses,

With increased study of bio-adhesives, a significant effort has been made in search for novel adhesives that will combine reversibility, repeated usage, stronger bonds and faster bonding time, non-toxic, and more importantly be effective in wet and other extreme conditions.

A team of Korean scientists-made up of scientists from Korea Institute of Science and Technology (KIST) and UNIST has recently found a way to make building flexible pressure sensors easier–by mimicking the suction cups on octopus’s tentacles.

A July 5, 2016 UNIST (Ulsan National Institute of Science and Technology) press release, which originated the news item, provides more information,

According to the research team, “Although flexible pressure sensors might give future prosthetics and robots a better sense of touch, building them requires a lot of laborious transferring of nano- and microribbons of inorganic semiconductor materials onto polymer sheets.”

In search of an easier way to process this transfer printing, Prof. Hyunhyub Ko (School of Energy and Chemical Engineering, UNIST) and his colleagues turned to the octopus suction cups for inspiration.

An octopus uses its tentacles to move to a new location and uses suction cups underneath each tentacle to grab onto something. Each suction cup contains a cavity whose pressure is controlled by surrounding muscles. These can be made thinner or thicker on demand, increasing or decreasing air pressure inside the cup, allowing for sucking and releasing as desired.

By mimicking muscle actuation to control cavity-pressure-induced adhesion of octopus suckers, Prof. Ko and his team engineered octopus-inspired smart adhesive pads. They used the rubbery material polydimethylsiloxane (PDMS) to create an array of microscale suckers, which included pores that are coated with a thermally responsive polymer to create sucker-like walls.

The team discovered that the best way to replicate organic nature of muscle contractions would be through applied heat. Indeed, at room temperature, the walls of each pit sit in an ‘open’ state, but when the mat is heated to 32°C, the walls contract, creating suction, therby allowing the entire mate to adhere to a material (mimicking the suction function of an octopus). The adhesive strength also spiked from .32 kilopascals to 94 kilopascals at high temperature.

The team reports that the mat worked as envisioned—they made some indium gallium arsenide transistors that sat on a flexible substrate and also used it to move some nanomaterials to a different type of flexible material.

Prof. Ko and his team expect that their smart adhesive pads can be used as the substrate for wearable health sensors, such as Band-Aids or sensors that stick to the skin at normal body temperatures but fall off when rinsed under cold water.

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

Octopus-Inspired Smart Adhesive Pads for Transfer Printing of Semiconducting Nanomembranes by Hochan Lee, Doo-Seung Um, Youngsu Lee, Seongdong Lim, Hyung-jun Kim,  and Hyunhyub Ko. Advanced Materials DOI: 10.1002/adma.201601407 Version of Record online: 20 JUN 2016

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

An easier, cheaper way to diagnose Ebola

A Sept. 9, 2015 news item on Nanotechnology Now highlights a new technology for diagnosing the Ebola virus,

A new Ebola test that uses magnetic nanoparticles could help curb the spread of the disease in western Africa. Research published in Biosensors and Bioelectronics shows that the new test is 100 times more sensitive than the current test, and easier to use. Because of this, the new test makes it easier and cheaper to diagnose cases, enabling healthcare workers to isolate patients and prevent the spread of Ebola.

The authors of the study, from the Chinese Academy of Sciences, say their new technology could be applied to the detection of any biological molecules, making it useful to diagnose other infectious diseases, like flu, and potentially detect tumors and even contamination in wastewater.

A Sept. 9, 2015 Elsevier press release, which originated the news item, provides more detail,

The Ebola virus causes an acute illness that is deadly in half of all cases, on average. The current outbreak of Ebola, which started in March 2014, affects countries in west Africa. In the most severely affected countries, like Guinea, Liberia and Sierra Leone, resources are limited, making control of the outbreak challenging. There is no vaccine for Ebola, so detecting the virus is key to controlling the outbreak: with an accurate diagnosis, patients can be isolated and treated properly, reducing the risk of spread.

“In west Africa, resources are under pressure, so complicated, expensive tests are not very helpful,” said Professor Xiyun Yan, one of the authors of the study from the Chinese Academy of Sciences. “Our new strip test is a simple, one-step test that is cheap and easy to use, and provides a visible signal, which means people don’t need training to use it. We think it will be especially helpful in rural areas, where technical equipment and skills are not available.”

Currently there are two ways to test for the Ebola virus: using a method called polymerase chain reaction (PCR), which makes copies of the molecules for detection, and with antibody-capture enzyme-linked immunosorbent assay (ELISA), which gives a visual indication when a given molecule is in a sample. PCR is very sensitive, but is expensive and complicated, requiring special skills and technical equipment. The ELISA – or gold strip test – is cheaper but sensitivity is very low, which means it often gives the wrong results.

The new test, called the nanozyme test, uses magnetic nanoparticles, which work like enzymes to make the signal stronger, giving a clearer result you can see with the naked eye. The test can detect much smaller amounts of the virus, and is 100 times more sensitive than the gold strip test.

“People have loved the strip test for many years, but it has a major weakness: it’s not sensitive enough. We’re very excited about our new nanozyme test, as it is much more sensitive and you don’t need any specialist equipment to get a quick, accurate result,” said Dr. Yan.

Strip tests work by attaching molecules called antibodies to gold particles to look for a particular molecule in a sample. When they attach to the molecule you’re looking for, in this case a virus, they produce a signal, such as a color change. In order to find the virus, the particles need to be labelled with enzymes, which speed up detection and signalling.

With the new nanozyme test, the researchers applied magnetic nanoparticles as a nanozyme probe in place of gold nanoparticles. After labeling with an antibody that attaches to the Ebola virus, this novel probe is able to recognize and separate the virus in a sample. The nanoparticles are magnetic, so to concentrate the virus particles in a sample, all you need to do is hold the sample against a magnet; no expensive equipment is needed.

The nanozyme test is 100 times more sensitive than the gold strip test, detecting molecules called glycoproteins on the surface of the Ebola virus at concentrations as low as 1 nanogram per milliliter.

The researchers have applied for a patent for the new test, which is currently being taken to west Africa by the CDC to use in the field. The researchers are also collaborating with clinical teams to apply the technology to other diseases, and with a company that treats wastewater to see if it can help remove environmental contamination.

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

Nanozyme-strip for rapid local diagnosis of Ebola by Demin Duan, Kelong Fan, Dexi Zhang, Shuguang Tan, Mifang Liang, Yang Liu, Jianlin Zhang, Panhe Zhang, Wei Liu, Xiangguo Qiu, Gary P. Kobinger, George Fu Gao, Xiyun Yan. Biosensors and Bioelectronics Volume 74, 15 December 2015, Pages 134–141 doi:10.1016/j.bios.2015.05.025

This paper appears to be open access.

Bringing the Nanoworld Together Workshop in Beijing, China, Sept. 24 – 25, 2014

The speakers currently confirmed for the ‘Bringing the Nanoworld Together Workshop organized by Oxford Instruments are from the UK, China, Canada, the US, and the Netherlands as per a July 2, 2014 news item on Nanowerk (Note: A link has been removed),

‘Bringing the Nanoworld Together’ is an event organised by Oxford Instruments to share the expertise of scientists in the field of Nanotechnology. It will be hosted at the IOS-CAS [Institute of Semiconductors-Chinese Academy of Sciences] Beijing.

Starting with half day plenary sessions on 2D materials with guest plenary speaker Dr Aravind Vijayaraghavan from the National Graphene Institute in Manchester, UK, and on Quantum Information Processing with guest plenary speaker Prof David Cory from the Institute for Quantum Computing, University of Waterloo, Canada, Oxford Instruments’ seminar at the IOP in Beijing from 24-25th September [2014] promises to discuss cutting edge nanotechnology solutions for multiple applications.

A July 1, 2014 Oxford Instruments press release, which originated the news item, describes the sessions and provides more details about the speakers,

Two parallel sessions will focus on thin film processing, & materials characterisation, surface science and cryogenic environments and a wide range of topics will be covered within each technical area. These sessions will include guest international and Chinese speakers from renowned research institutions, speakers from the host institute, and technical experts from Oxford Instruments. This will also present an excellent opportunity for networking between all participants.

Confirmed speakers include the following, but more will be announced soon:

Dr. Aravind Vijayaraghavan, National Graphene Institute, Manchester, UK
Prof David Cory, Institute for Quantum Computing, University of Waterloo, Canada
Prof Guoxing Miao, Institute for Quantum Computing, University of Waterloo, Canada
Prof. HE Ke, Tsinghua University, Institute of Physics, CAS, China
Dr. WANG Xiaodong, Institute of Semiconductors, CAS, China
Prof Erwin Kessels, Tue Eindhoven, Netherlands
Prof. ZENG Yi, Institute of Semiconductor, CAS, China
Prof Robert Klie, University of Illinois Chicago, USA
Prof. Xinran WANG, Nanjing University, China
Prof. Zhihai CHENG, National Centre for Nanoscience and Technology, China
Prof. Yeliang WANG, Institute of Physics, CAS, China

The thin film processing sessions will review latest etch and deposition technological advances, including: ALD, Magnetron Sputtering, ICP PECVD, Nanoscale Etch, MEMS, MBE and more.

Materials characterisation, Surface Science and Cryogenic Environment sessions will cover multiple topics and technologies including: Ultra high vacuum SPM, Cryo free low temperature solutions, XPS/ESCA, an introduction to atomic force microscopy (AFM) and applications such as nanomechanics, In-situ heating and tensile characterisation using EBSD, Measuring Layer thicknesses and compositions using EDS, Nanomanipulation and fabrication within the SEM / FIB.

The host of last year’s Nanotechnology Tools seminar in India, Prof. Rudra Pratap, Chairperson at the Centre for Nano Science and Engineering, Indian Institute of Science, IISC Bangalore commented, “This seminar has been extremely well organised with competent speakers covering a variety of processes and tools for nanofabrication. It is great to have practitioners of the art give talks and provide tips and solutions based on their experience, something that cannot be found in text books.”

“This workshop is a great opportunity for a wide range of scientists in research and manufacturing to discover practical aspects of many new and established processes, technologies and applications, directly from renowned scientists and a leading manufacturer with over 50 years in the industry”, comments Mark Sefton, Sector Head of Oxford Instruments NanoSolutions, “Delegates appreciate the informal workshop atmosphere of these events, encouraging delegates to participate through open discussion and sharing their questions and experiences.”

This seminar is free of charge but prior booking is essential.

You can register on the Oxford Instruments website’s Bringing the Nanoworld Together Workshop webpage,

Ferroelectric switching in the lung, heart, and arteries

A June 23, 2014 University of Washington (state) news release (also on EurekAlert) describes how the human body (and other biological tissue) is capable of generating ferroelectricity,

University of Washington researchers have shown that a favorable electrical property is present in a type of protein found in organs that repeatedly stretch and retract, such as the lungs, heart and arteries. These findings are the first that clearly track this phenomenon, called ferroelectricity, occurring at the molecular level in biological tissues.

The news release gives a brief description of ferroelectricity and describes the research team’s latest work with biological tissues,

Ferroelectricity is a response to an electric field in which a molecule switches from having a positive to a negative charge. This switching process in synthetic materials serves as a way to power computer memory chips, display screens and sensors. This property only recently has been discovered in animal tissues and researchers think it may help build and support healthy connective tissues in mammals.

A research team led by Li first discovered ferroelectric properties in biological tissues in 2012, then in 2013 found that glucose can suppress this property in the body’s connective tissues, wherever the protein elastin is present. But while ferroelectricity is a proven entity in synthetic materials and has long been thought to be important in biological functions, its actual existence in biology hasn’t been firmly established.

This study proves that ferroelectric switching happens in the biological protein elastin. When the researchers looked at the base structures within the protein, they saw similar behavior to the unit cells of solid-state materials, where ferroelectricity is well understood.

“When we looked at the smallest structural unit of the biological tissue and how it was organized into a larger protein fiber, we then were able to see similarities to the classic ferroelectric model found in solids,” Li said.

The researchers wanted to establish a more concrete, precise way of verifying ferroelectricity in biological tissues. They used small samples of elastin taken from a pig’s aorta and poled the tissues using an electric field at high temperatures. They then measured the current with the poling field removed and found that the current switched direction when the poling electric field was switched, a sign of ferroelectricity.

They did the same thing at room temperature using a laser as the heat source, and the current also switched directions.

Then, the researchers tested for this behavior on the smallest-possible unit of elastin, called tropoelastin, and again observed the phenomenon. They concluded that this switching property is “intrinsic” to the molecular make-up of elastin.

The next step is to understand the biological and physiological significance of this property, Li said. One hypothesis is that if ferroelectricity helps elastin stay flexible and functional in the body, a lack of it could directly affect the hardening of arteries.

“We may be able to use this as a very sensitive technique to detect the initiation of the hardening process at a very early stage when no other imaging technique will be able to see it,” Li said.

The team also is looking at whether this property plays a role in normal biological functions, perhaps in regulating the growth of tissue.

Co-authors are Pradeep Sharma at the University of Houston, Yanhang Zhang at Boston University, and collaborators at Nanjing University and the Chinese Academy of Sciences.

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

Ferroelectric switching of elastin by Yuanming Liu, Hong-Ling Cai, Matthew Zelisko, Yunjie Wang, Jinglan Sun, Fei Yan, Feiyue Ma, Peiqi Wang, Qian Nataly Chen, Hairong Zheng, Xiangjian Meng, Pradeep Sharma, Yanhang Zhang, and Jiangyu Li. Proceedings of the National Academy of Sciences (PNAS) doi: 10.1073/pnas.1402909111

This paper is behind a paywall.

I think this is a new practice. There is a paragraph on the significance of this work (follow the link to the paper),

Ferroelectricity has long been speculated to have important biological functions, although its very existence in biology has never been firmly established. Here, we present, to our knowledge, the first macroscopic observation of ferroelectric switching in a biological system, and we elucidate the origin and mechanism underpinning ferroelectric switching of elastin. It is discovered that the polarization in elastin is intrinsic at the monomer level, analogous to the unit cell level polarization in classical perovskite ferroelectrics. Our findings settle a long-standing question on ferroelectric switching in biology and establish ferroelectricity as an important biophysical property of proteins. We believe this is a critical first step toward resolving its physiological significance and pathological implications.

Should October 2013 be called ‘the month of graphene’?

Since the Oct. 10-11, 2013 Graphene Flagship (1B Euros investment) launch, mentioned in my preview Oct. 7, 2013 posting, there’ve been a flurry of graphene-themed news items both on this blog and elsewhere and I’ve decided to offer a brief roundup what I’ve found elsewhere.

Dexter Johnson offers a commentary in the pithily titled, Europe Invests €1 Billion to Become “Graphene Valley,” an Oct. 15, 2013 posting on his Nanoclast blog (on the IEEE [Institute of Electrical and Electronics Engineers] website) Note: Links have been removed,

The initiative has been dubbed “The Graphene Flagship,” and apparently it is the first in a number of €1 billion, 10-year plans the EC is planning to launch. The graphene version will bring together 76 academic institutions and industrial groups from 17 European countries, with an initial 30-month-budget of €54M ($73 million).

Graphene research is still struggling to find any kind of applications that will really take hold, and many don’t expect it will have a commercial impact until 2020. What’s more, manufacturing methods are still undeveloped. So it would appear that a 10-year plan is aimed at the academic institutions that form the backbone of this initiative rather than commercial enterprises.

Just from a political standpoint the choice of Chalmers University in Sweden as the base of operations for the Graphene Flagship is an intriguing choice. …

I have to agree with Dexter that choosing Chalmers University over the University of Manchester where graphene was first isolated is unexpected. As a companion piece to reading Dexter’s posting in its entirety and which features a video from the flagship launch, you might want to try this Oct. 15, 2013 article by Koen Mortelmans for Youris (h/t Oct. 15, 2013 news item on Nanowerk),

Andre Konstantin Geim is the only person who ever received both a Nobel and an Ig Nobel. He was born in 1958 in Russia, and is a Dutch-British physicist with German, Polish, Jewish and Ukrainian roots. “Having lived and worked in several European countries, I consider myself European. I don’t believe that any further taxonomy is necessary,” he says. He is now a physics professor at the University of Manchester. …

He shared the Noble [Nobel] Prize in 2010 with Konstantin Novoselov for their work on graphene. It was following on their isolation of microscope visible grapheme flakes that the worldwide research towards practical applications of graphene took off.  “We did not invent graphene,” Geim says, “we only saw what was laid up for five hundred year under our noses.”

Geim and Novoselov are often thought to have succeeded in separating graphene from graphite by peeling it off with ordinary duct tape until there only remained a layer. Graphene could then be observed with a microscope, because of the partial transparency of the material. That is, after dissolving the duct tape material in acetone, of course. That is also the story Geim himself likes to tell.

However, he did not use – as the urban myth goes – graphite from a common pencil. Instead, he used a carbon sample of extreme purity, specially imported. He also used ultrasound techniques. But, probably the urban legend will survive, as did Archimedes’ bath and Newtons apple. “It is nice to keep some of the magic,” is the expression Geim often uses when he does not want a nice story to be drowned in hard facts or when he wants to remain discrete about still incomplete, but promising research results.

Mortelmans’ article fills in some gaps for those not familiar with the graphene ‘origins’ story while Tim Harper’s July 22, 2012 posting on Cientifica’s (an emerging technologies consultancy where Harper is the CEO and founder) TNT blog offers an insight into Geim’s perspective on the race to commercialize graphene with a paraphrased quote for the title of Harper’s posting, “It’s a bit silly for society to throw a little bit of money at (graphene) and expect it to change the world.” (Note: Within this context, mention is made of the company’s graphene opportunities report.)

With all this excitement about graphene (and carbon generally), the magazine titled Carbon has just published a suggested nomenclature for 2D carbon forms such as graphene, graphane, etc., according to an Oct. 16, 2013 news item on Nanowerk (Note: A link has been removed),

There has been an intense research interest in all two-dimensional (2D) forms of carbon since Geim and Novoselov’s discovery of graphene in 2004. But as the number of such publications rise, so does the level of inconsistency in naming the material of interest. The isolated, single-atom-thick sheet universally referred to as “graphene” may have a clear definition, but when referring to related 2D sheet-like or flake-like carbon forms, many authors have simply defined their own terms to describe their product.

This has led to confusion within the literature, where terms are multiply-defined, or incorrectly used. The Editorial Board of Carbon has therefore published the first recommended nomenclature for 2D carbon forms (“All in the graphene family – A recommended nomenclature for two-dimensional carbon materials”).

This proposed nomenclature comes in the form of an editorial, from Carbon (Volume 65, December 2013, Pages 1–6),

All in the graphene family – A recommended nomenclature for two-dimensional carbon materials

  • Alberto Bianco
    CNRS, Institut de Biologie Moléculaire et Cellulaire, Immunopathologie et Chimie Thérapeutique, Strasbourg, France
  • Hui-Ming Cheng
    Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, 72 Wenhua Road, Shenyang 110016, China
  • Toshiaki Enoki
    Department of Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology, Tokyo, Japan
  • Yury Gogotsi
    Materials Science and Engineering Department, A.J. Drexel Nanotechnology Institute, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104, USA
  • Robert H. Hurt
    Institute for Molecular and Nanoscale Innovation, School of Engineering, Brown University, Providence, RI 02912, USA
  • Nikhil Koratkar
    Department of Mechanical, Aerospace and Nuclear Engineering, The Department of Materials Science and Engineering, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY 12180, USA
  • Takashi Kyotani
    Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan
  • Marc Monthioux
    Centre d’Elaboration des Matériaux et d’Etudes Structurales (CEMES), UPR-8011 CNRS, Université de Toulouse, 29 Rue Jeanne Marvig, F-31055 Toulouse, France
  • Chong Rae Park
    Carbon Nanomaterials Design Laboratory, Global Research Laboratory, Research Institute of Advanced Materials, Department of Materials Science and Engineering, Seoul National University, Seoul 151-744, Republic of Korea
  • Juan M.D. Tascon
    Instituto Nacional del Carbón, INCAR-CSIC, Apartado 73, 33080 Oviedo, Spain
  • Jin Zhang
    Center for Nanochemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China

This editorial is behind a paywall.

Danish Chinese collaboration on graphene project could lead to smaller, faster, greener electronic devices

A mixed team of Danish and Chinese scientists have made a transistor from a single molecular monolayer that works on a computer chip according to a June 19, 2013 University of Copenhagen news release,

The molecular integrated circuit was created by a group of chemists and physicists from the Department of Chemistry Nano-Science Center at the University of Copenhagen and Chinese Academy of Sciences, Beijing. Their discovery “Ultrathin Reduced Graphene Oxide Films as Transparent Top-Contacts for Light Switchable Solid-State Molecular Junctions”  has just been published online in the prestigious periodical Advanced Materials. The breakthrough was made possible through an innovative use of the two dimensional carbon material graphene.

Here’s how the transistor works (from the news release),

The molecular computer chip is a sandwich built with one layer of gold, one of molecular components and one of the extremely thin carbon material graphene. The molecular transistor in the sandwich is switched on and of using a light impulse so one of the peculiar properties of graphene is highly useful. Even though graphene is made of carbon, it’s almost completely translucent.

Using the new graphene chip researchers can now place their molecules with great precision. This makes it faster and easier to test the functionality of molecular wires, contacts and diodes so that chemists will know in no time whether they need to get back to their beakers to develop new functional molecules, explains Nørgaard [Kasper Nørgaard, an associate professor in chemistry at the University of Copenhagen].

“We’ve made a design, that’ll hold many different types of molecule” he says and goes on: “Because the graphene scaffold is closer to real chip design it does make it easier to test components, but of course it’s also a step on the road to making a real integrated circuit using molecular components. And we must not lose sight of the fact that molecular components do have to end up in an integrated circuit, if they are going to be any use at all in real life”.

In addition to the other benefits of this graphene chip, greater precision, etc., it is also greener, requiring no rare earths or heavy metals.

If you have problems accessing the news release, you can find the information in a June 20, 2013 news item on Nanowerk.

Self-assembling, size-specific nanopores or nanotubes mimic nature

I guess you can call this biomimicry or biomimetics as it’s also known. From the  State University of New York at Buffalo  July 17, 2012 news releaseby Charlotte Hsu,

Inspired by nature, an international research team has created synthetic pores that mimic the activity of cellular ion channels, which play a vital role in human health by severely restricting the types of materials allowed to enter cells.

The pores the scientists built are permeable to potassium ions and water, but not to other ions such as sodium and lithium ions.

This kind of extreme selectivity, while prominent in nature, is unprecedented for a synthetic structure, said University at Buffalo chemistry professor Bing Gong, PhD, who led the study.

Here’s how they did it (from the news release),

To create the synthetic pores, the researchers developed a method to force donut-shaped molecules called rigid macrocycles to pile on top of one another. [emphasis mine] The scientists then stitched these stacks of molecules together using hydrogen bonding. The resulting structure was a nanotube with a pore less than a nanometer in diameter.

The July 17, 2012 media advisory by Tona Kunz from the Argonne National Laboratory (one of the partners in this research) describes why creating consistently sized nanopores/nanotubes has been so difficult and offers more information about the macrocycles,

Nanopores and their rolled up version, nanotubes, consist of atoms bonded to each other in a hexagonal pattern to create an array of nanometer-scale openings or channels. This structure creates a filter that can be sized to select which molecules and ions pass into drinking water or into a cell. The same filter technique can limit the release of chemical by-products from industrial processes.

Successes in making synthetic nanotubes from various materials have been reported previously, but their use has been limited because they degrade in water, the pore size of water-resistant carbon nanotubes is difficult to control, and, more critically, the inability to assemble them into appropriate filters.

An international team of researchers, with help of the Advanced Photon Source at Argonne National Laboratory, have succeeded in overcoming these hurdles by building self-assembling, size-specific nanopores. This new capability enables them to engineer nanotubes for specific functions and use pore size to selectively block specific molecules and ions.

Scientists used groupings of atoms called ridged macrocycles that share a planar hexahenylene ethynylene core that bears six amide side chains. Through a cellular self-assembly process, the macrocycles stack cofacially, or atom on top of atom. Each layer of the macrocycle is held together by bonding among hydrogen atoms in the amide side chains. This alignment creates a uniform pore size regardless of the length of the nanotube. A slight misalignment of even a few macrocycles can alter the pore size and greatly compromise the nanotube’s functionality.

Here’s an image of the macrocycles supplied by the Agronne National Labortory,

A snapshot of a helical stack of macryocycles generated in the computer simulation.

The size specificity is  important if  nanopores/nanotubes are going to be used in medical applications,

The pore sizes can be adjusted to filter molecules and ions according to their size by changing the macroycle size, akin to the way a space can be put into a wedding ring to make it fit tighter. The channels are permeable to water, which aids in the fast transmission of intercellular information. The synthetic nanopores mimic the activity of cellular ion channels used in the human body. The research lays the foundation for an array of exciting new technology, such as new ways to deliver directly into cells proteins or medicines to fight diseases.

The research group’s paper has appeared in Nature Communications as of July 17, 2012, from Hsu’s news release,

The study’s lead authors are Xibin Zhou of Beijing Normal University; Guande Liu of Shanghai Jiao Tong University; Kazuhiro Yamato, postdoctoral scientist at UB; and Yi Shen of Shanghai Jiao Tong University and the Shanghai Institute of Applied Physics, Chinese Academy of Sciences. Other institutions that contributed to the work include the University of Nebraska-Lincoln and Argonne National Laboratory. Frank Bright, a SUNY Distinguished Professor of chemistry at UB, assisted with spectroscopic studies.