Category Archives: nanotechnology

Genes, intelligence, Chinese CRISPR (clustered regularly interspaced short palindromic repeats) babies, and other children

This started out as an update and now it’s something else. What follows is a brief introduction to the Chinese CRISPR twins; a brief examination of parents, children, and competitiveness; and, finally, a suggestion that genes may not be what we thought. I also include a discussion about how some think scientists should respond when they know beforehand that one of their kin is crossing an ethical line. Basically, this is a complex topic and I am attempting to interweave a number of competing lines of query into one narrative about human nature and the latest genetics obsession.

Introduction to the Chinese CRISPR twins

Back in November 2018 I covered the story about the Chinese scientist, He Jiankui , who had used CRISPR technology to edit genes in embryos that were subsequently implanted in a waiting mother (apparently there could be as many as eight mothers) with the babies being brought to term despite an international agreement (of sorts) not to do that kind of work. At this time, we know of the twins, Lulu and Nana but, by now, there may be more babies. (I have much more detail about the initial controversies in my November 28, 2018 posting.)

It seems the drama has yet to finish unfolding. There may be another consequence of He’s genetic tinkering.

Could the CRISPR babies, Lulu and Nana, have enhanced cognitive abilities?

Yes, according to Antonio Regalado’s February 21, 2019 article (behind a paywall) for MIT’s (Massachusetts Institute of Technology) Technology Review, those engineered babies may have enhanced abilities for learning and remembering.

For those of us who can’t get beyond the paywall, others have been successful. Josh Gabbatiss in his February 22, 2019 article for independent.co.uk provides some detail,

The world’s first gene edited babies may have had their brains unintentionally altered – and perhaps cognitively enhanced – as a result of the controversial treatment undertaken by a team of Chinese scientists.

Dr He Jiankui and his team allegedly deleted a gene from a number of human embryos before implanting them in their mothers, a move greeted with horror by the global scientific community. The only known successful birth so far is the case of twin girls Nana and Lulu.

The now disgraced scientist claimed that he removed a gene called CCR5 [emphasis mine] from their embroyos in an effort to make the twins resistant to infection by HIV.

But another twist in the saga has now emerged after a new paper provided more evidence that the impact of CCR5 deletion reaches far beyond protection against dangerous viruses – people who naturally lack this gene appear to recover more quickly from strokes, and even go further in school. [emphasis mine]

Dr Alcino Silva, a neurobiologist at the University of California, Los Angeles, who helped identify this role for CCR5 said the work undertaken by Dr Jiankui likely did change the girls’ brains.

“The simplest interpretation is that those mutations will probably have an impact on cognitive function in the twins,” he told the MIT Technology Review.

The connection immediately raised concerns that the gene was targeted due to its known links with intelligence, which Dr Silva said was his immediate response when he heard the news.

… there is no evidence that this was Dr Jiankui’s goal and at a press conference organised after the initial news broke, he said he was aware of the work but was “against using genome editing for enhancement”.

..

Claire Maldarelli’s February 22, 2019 article for Popular Science provides more information about the CCR5 gene/protein (Note: Links have been removed),

CCR5 is a protein that sits on the surface of white blood cells, a major component of the human immune system. There, it allows HIV to enter and infect a cell. A chunk of the human population naturally carries a mutation that makes CCR5 nonfunctional (one study found that 10 percent of Europeans have this mutation), which often results in a smaller protein size and one that isn’t located on the outside of the cell, preventing HIV from ever entering and infecting the human immune system.

The goal of the Chinese researchers’ work, led by He Jiankui of the Southern University of Science and Technology located in Shenzhen, was to tweak the embryos’ genome to lack CCR5, ensuring the babies would be immune to HIV.

But genetics is rarely that simple.

In recent years, the CCR5 gene has been a target of ongoing research, and not just for its relationship to HIV. In an attempt to understand what influences memory formation and learning in the brain, a group of researchers at UCLA found that lowering the levels of CCR5 production enhanced both learning and memory formation. This connection led those researchers to think that CCR5 could be a good drug target for helping stroke victims recover: Relearning how to move, walk, and talk is a key component to stroke rehabilitation.

… promising research, but it begs the question: What does that mean for the babies who had their CCR5 genes edited via CRISPR prior to their birth? Researchers speculate that the alternation will have effects on the children’s cognitive functioning. …

John Loeffler’s February 22, 2019 article for interestingengineering.com notes that there are still many questions about He’s (scientist’s name) research including, did he (pronoun) do what he claimed? (Note: Links have been removed),

Considering that no one knows for sure whether He has actually done as he and his team claim, the swiftness of the condemnation of his work—unproven as it is—shows the sensitivity around this issue.

Whether He did in fact edit Lulu and Nana’s genes, it appears he didn’t intend to impact their cognitive capacities. According to MIT Technology Review, not a single researcher studying CCR5’s role in intelligence was contacted by He, even as other doctors and scientists were sought out for advice about his project.

This further adds to the alarm as there is every expectation that He should have known about the connection between CCR5 and cognition.

At a gathering of gene-editing researchers in Hong Kong two days after the birth of the potentially genetically-altered twins was announced, He was asked about the potential impact of erasing CCR5 from the twins DNA on their mental capacity.

He responded that he knew about the potential cognitive link shown in Silva’s 2016 research. “I saw that paper, it needs more independent verification,” He said, before adding that “I am against using genome editing for enhancement.”

The problem, as Silva sees it, is that He may be blazing the trail for exactly that outcome, whether He intends to or not. Silva says that after his 2016 research was published, he received an uncomfortable amount of attention from some unnamed, elite Silicon Valley leaders who seem to be expressing serious interest in using CRISPR to give their children’s brains a boost through gene editing. [emphasis mine]

As such, Silva can be forgiven for not quite believing He’s claims that he wasn’t intending to alter the human genome for enhancement. …

The idea of designer babies isn’t new. As far back as Plato, the thought of using science to “engineer” a better human has been tossed about, but other than selective breeding, there really hasn’t been a path forward.

In the late 1800s, early 1900s, Eugenics made a real push to accomplish something along these lines, and the results were horrifying, even before Nazism. After eugenics mid-wifed the Holocaust in World War II, the concept of designer children has largely been left as fodder for science fiction since few reputable scientists would openly declare their intention to dabble in something once championed and pioneered by the greatest monsters of the 20th century.

Memories have faded though, and CRISPR significantly changes this decades-old calculus. CRISPR makes it easier than ever to target specific traits in order to add or subtract them from an embryos genetic code. Embryonic research is also a diverse enough field that some scientist could see pioneering designer babies as a way to establish their star power in academia while getting their names in the history books, [emphasis mine] all while working in relative isolation. They only need to reveal their results after the fact and there is little the scientific community can do to stop them, unfortunately.

When He revealed his research and data two days after announcing the births of Lulu and Nana, the gene-scientists at the Hong Kong conference were not all that impressed with the quality of He’s work. He has not provided access for fellow researchers to either his data on Lulu, Nana, and their family’s genetic data so that others can verify that Lulu and Nana’s CCR5 genes were in fact eliminated.

This almost rudimentary verification and validation would normally accompany a major announcement such as this. Neither has He’s work undergone a peer-review process and it hasn’t been formally published in any scientific journal—possibly for good reason.

Researchers such as Eric Topol, a geneticist at the Scripps Research Institute, have been finding several troubling signs in what little data He has released. Topol says that the editing itself was not precise and show “all kinds of glitches.”

Gaetan Burgio, a geneticist at the Australian National University, is likewise unimpressed with the quality of He’s work. Speaking of the slides He showed at the conference to support his claim, Burgio calls it amateurish, “I can believe that he did it because it’s so bad.”

Worse of all, its entirely possible that He actually succeeded in editing Lulu and Nana’s genetic code in an ad hoc, unethical, and medically substandard way. Sadly, there is no shortage of families with means who would be willing to spend a lot of money to design their idea of a perfect child, so there is certainly demand for such a “service.”

It’s nice to know (sarcasm icon) that the ‘Silicon Valley elite’ are willing to volunteer their babies for scientific experimentation in a bid to enhance intelligence.

The ethics of not saying anything

Natalie Kofler, a molecular biologist, wrote a February 26, 2019 Nature opinion piece and call to action on the subject of why scientists who were ‘in the know’ remained silent about He’s work prior to his announcements,

Millions [?] were shocked to learn of the birth of gene-edited babies last year, but apparently several scientists were already in the know. Chinese researcher He Jiankui had spoken with them about his plans to genetically modify human embryos intended for pregnancy. His work was done before adequate animal studies and in direct violation of the international scientific consensus that CRISPR–Cas9 gene-editing technology is not ready or appropriate for making changes to humans that could be passed on through generations.

Scholars who have spoken publicly about their discussions with He described feeling unease. They have defended their silence by pointing to uncertainty over He’s intentions (or reassurance that he had been dissuaded), a sense of obligation to preserve confidentiality and, perhaps most consistently, the absence of a global oversight body. Others who have not come forward probably had similar rationales. But He’s experiments put human health at risk; anyone with enough knowledge and concern could have posted to blogs or reached out to their deans, the US National Institutes of Health or relevant scientific societies, such as the Association for Responsible Research and Innovation in Genome Editing (see page 440). Unfortunately, I think that few highly established scientists would have recognized an obligation to speak up.

I am convinced that this silence is a symptom of a broader scientific cultural crisis: a growing divide between the values upheld by the scientific community and the mission of science itself.

A fundamental goal of the scientific endeavour is to advance society through knowledge and innovation. As scientists, we strive to cure disease, improve environmental health and understand our place in the Universe. And yet the dominant values ingrained in scientists centre on the virtues of independence, ambition and objectivity. That is a grossly inadequate set of skills with which to support a mission of advancing society.

Editing the genes of embryos could change our species’ evolutionary trajectory. Perhaps one day, the technology will eliminate heritable diseases such as sickle-cell anaemia and cystic fibrosis. But it might also eliminate deafness or even brown eyes. In this quest to improve the human race, the strengths of our diversity could be lost, and the rights of already vulnerable populations could be jeopardized.

Decisions about how and whether this technology should be used will require an expanded set of scientific virtues: compassion to ensure its applications are designed to be just, humility to ensure its risks are heeded and altruism to ensure its benefits are equitably distributed.

Calls for improved global oversight and robust ethical frameworks are being heeded. Some researchers who apparently knew of He’s experiments are under review by their universities. Chinese investigators have said He skirted regulations and will be punished. But punishment is an imperfect motivator. We must foster researchers’ sense of societal values.

Fortunately, initiatives popping up throughout the scientific community are cultivating a scientific culture informed by a broader set of values and considerations. The Scientific Citizenship Initiative at Harvard University in Cambridge, Massachusetts, trains scientists to align their research with societal needs. The Summer Internship for Indigenous Peoples in Genomics offers genomics training that also focuses on integrating indigenous cultural perspectives into gene studies. The AI Now Institute at New York University has initiated a holistic approach to artificial-intelligence research that incorporates inclusion, bias and justice. And Editing Nature, a programme that I founded, provides platforms that integrate scientific knowledge with diverse cultural world views to foster the responsible development of environmental genetic technologies.

Initiatives such as these are proof [emphasis mine] that science is becoming more socially aware, equitable and just. …

I’m glad to see there’s work being done on introducing a broader set of values into the scientific endeavour. That said, these programmes seem to be voluntary, i.e., people self-select, and those most likely to participate in these programmes are the ones who might be inclined to integrate social values into their work in the first place.

This doesn’t address the issue of how to deal with unscrupulous governments pressuring scientists to create designer babies along with hypercompetitive and possibly unscrupulous individuals such as the members of the ‘Silicon Valley insiders mentioned in Loeffler’s article, teaming up with scientists who will stop at nothing to get their place in the history books.

Like Kofler, I’m encouraged to see these programmes but I’m a little less convinced that they will be enough. What form it might take I don’t know but I think something a little more punitive is also called for.

CCR5 and freedom from HIV

I’ve added this piece about the Berlin and London patients because, back in November 2018, I failed to realize how compelling the idea of eradicating susceptibility to AIDS/HIV might be. Reading about some real life remissions helped me to understand some of He’s stated motivations a bit better. Unfortunately, there’s a major drawback described here in a March 5, 2019 news item on CBC (Canadian Broadcasting Corporation) online news attributed to Reuters,

An HIV-positive man in Britain has become the second known adult worldwide to be cleared of the virus that causes AIDS after he received a bone marrow transplant from an HIV-resistant donor, his doctors said.

The therapy had an early success with a man known as “the Berlin patient,” Timothy Ray Brown, a U.S. man treated in Germany who is 12 years post-transplant and still free of HIV. Until now, Brown was the only person thought to have been cured of infection with HIV, the virus that causes AIDS.

Such transplants are dangerous and have failed in other patients. They’re also impractical to try to cure the millions already infected.

In the latest case, the man known as “the London patient” has no trace of HIV infection, almost three years after he received bone marrow stem cells from a donor with a rare genetic mutation that resists HIV infection — and more than 18 months after he came off antiretroviral drugs.

“There is no virus there that we can measure. We can’t detect anything,” said Ravindra Gupta, a professor and HIV biologist who co-led a team of doctors treating the man.

Gupta described his patient as “functionally cured” and “in remission,” but cautioned: “It’s too early to say he’s cured.”

Gupta, now at Cambridge University, treated the London patient when he was working at University College London. The man, who has asked to remain anonymous, had contracted HIV in 2003, Gupta said, and in 2012 was also diagnosed with a type of blood cancer called Hodgkin’s lymphoma.

In 2016, when he was very sick with cancer, doctors decided to seek a transplant match for him.

“This was really his last chance of survival,” Gupta told Reuters.

Doctors found a donor with a gene mutation known as CCR5 delta 32, which confers resistance to HIV. About one per cent of people descended from northern Europeans have inherited the mutation from both parents and are immune to most HIV. The donor had this double copy of the mutation.

That was “an improbable event,” Gupta said. “That’s why this has not been observed more frequently.”

Most experts say it is inconceivable such treatments could be a way of curing all patients. The procedure is expensive, complex and risky. To do this in others, exact match donors would have to be found in the tiny proportion of people who have the CCR5 mutation.

Specialists said it is also not yet clear whether the CCR5 resistance is the only key [emphasis mine] — or whether the graft-versus-host disease may have been just as important. Both the Berlin and London patients had this complication, which may have played a role in the loss of HIV-infected cells, Gupta said.

Not only is there some question as to what role the CCR5 gene plays, there’s also a question as to whether or not we know what role genes play.

A big question: are genes what we thought?

Ken Richardson’s January 3, 2019 article for Nautilus (I stumbled across it on May 14, 2019 so I’m late to the party) makes and supports a startling statement, It’s the End of the Gene As We Know It We are not nearly as determined by our genes as once thought (Note: A link has been removed),

We’ve all seen the stark headlines: “Being Rich and Successful Is in Your DNA” (Guardian, July 12); “A New Genetic Test Could Help Determine Children’s Success” (Newsweek, July 10); “Our Fortunetelling Genes” make us (Wall Street Journal, Nov. 16); and so on.

The problem is, many of these headlines are not discussing real genes at all, but a crude statistical model of them, involving dozens of unlikely assumptions. Now, slowly but surely, that whole conceptual model of the gene is being challenged.

We have reached peak gene, and passed it.

The preferred dogma started to appear in different versions in the 1920s. It was aptly summarized by renowned physicist Erwin Schrödinger in a famous lecture in Dublin in 1943. He told his audience that chromosomes “contain, in some kind of code-script, the entire pattern of the individual’s future development and of its functioning in the mature state.”

Around that image of the code a whole world order of rank and privilege soon became reinforced. These genes, we were told, come in different “strengths,” different permutations forming ranks that determine the worth of different “races” and of different classes in a class-structured society. A whole intelligence testing movement was built around that preconception, with the tests constructed accordingly.

The image fostered the eugenics and Nazi movements of the 1930s, with tragic consequences. Governments followed a famous 1938 United Kingdom education commission in decreeing that, “The facts of genetic inequality are something that we cannot escape,” and that, “different children … require types of education varying in certain important respects.”

Today, 1930s-style policy implications are being drawn once again. Proposals include gene-testing at birth for educational intervention, embryo selection for desired traits, identifying which classes or “races” are fitter than others, and so on. And clever marketizing now sees millions of people scampering to learn their genetic horoscopes in DNA self-testing kits.[emphasis mine]

So the hype now pouring out of the mass media is popularizing what has been lurking in the science all along: a gene-god as an entity with almost supernatural powers. Today it’s the gene that, in the words of the Anglican hymn, “makes us high and lowly and orders our estate.”

… at the same time, a counter-narrative is building, not from the media but from inside science itself.

So it has been dawning on us is that there is no prior plan or blueprint for development: Instructions are created on the hoof, far more intelligently than is possible from dumb DNA. That is why today’s molecular biologists are reporting “cognitive resources” in cells; “bio-information intelligence”; “cell intelligence”; “metabolic memory”; and “cell knowledge”—all terms appearing in recent literature.1,2 “Do cells think?” is the title of a 2007 paper in the journal Cellular and Molecular Life Sciences.3 On the other hand the assumed developmental “program” coded in a genotype has never been described.


It is such discoveries that are turning our ideas of genetic causation inside out. We have traditionally thought of cell contents as servants to the DNA instructions. But, as the British biologist Denis Noble insists in an interview with the writer Suzan Mazur,1 “The modern synthesis has got causality in biology wrong … DNA on its own does absolutely nothing [ emphasis mine] until activated by the rest of the system … DNA is not a cause in an active sense. I think it is better described as a passive data base which is used by the organism to enable it to make the proteins that it requires.”

I highly recommend reading Richardson’s article in its entirety. As well, you may want to read his book, ” Genes, Brains and Human Potential: The Science and Ideology of Intelligence .”

As for “DNA on its own doing absolutely nothing,” that might be a bit of a eye-opener for the Silicon Valley elite types investigating cognitive advantages attributed to the lack of a CCR5 gene. Meanwhile, there are scientists inserting a human gene associated with brain development into monkeys,

Transgenic monkeys and human intelligence

An April 2, 2019 news item on chinadaily.com describes research into transgenic monkeys,

Researchers from China and the United States have created transgenic monkeys carrying a human gene that is important for brain development, and the monkeys showed human-like brain development.

Scientists have identified several genes that are linked to primate brain size. MCPH1 is a gene that is expressed during fetal brain development. Mutations in MCPH1 can lead to microcephaly, a developmental disorder characterized by a small brain.

In the study published in the Beijing-based National Science Review, researchers from the Kunming Institute of Zoology, Chinese Academy of Sciences, the University of North Carolina in the United States and other research institutions reported that they successfully created 11 transgenic rhesus monkeys (eight first-generation and three second-generation) carrying human copies of MCPH1.

According to the research article, brain imaging and tissue section analysis showed an altered pattern of neuron differentiation and a delayed maturation of the neural system, which is similar to the developmental delay (neoteny) in humans.

Neoteny in humans is the retention of juvenile features into adulthood. One key difference between humans and nonhuman primates is that humans require a much longer time to shape their neuro-networks during development, greatly elongating childhood, which is the so-called “neoteny.”

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

Transgenic rhesus monkeys carrying the human MCPH1 gene copies show human-like neoteny of brain development by Lei Shi, Xin Luo, Jin Jiang, Yongchang Chen, Cirong Liu, Ting Hu, Min Li, Qiang Lin, Yanjiao Li, Jun Huang Hong Wang, Yuyu Niu, Yundi Shi, Martin Styner, Jianhong Wang, Yi Lu, Xuejin Sun, Hualin Yu, Weizhi Ji, Bing Su. National Science Review, nwz043, https://doi.org/10.1093/nsr/nwz043 Published: 27 March 2019

This appears to be an open access paper,

Transgenic monkeys and an ethical uproar

Predictably, this research set off alarms as Sharon Kirkey’s April 12, 2019 article for the National Post describes in detail (Note: A link has been removed)l,

Their brains may not be bigger than normal, but monkeys created with human brain genes are exhibiting cognitive changes that suggest they might be smarter — and the experiments have ethicists shuddering.

In the wake of the genetically modified human babies scandal, Chinese scientists [as a scientist from the US] are drawing fresh condemnation from philosophers and ethicists, this time over the announcement they’ve created transgenic monkeys with elements of a human brain.

Six of the monkeys died, however the five survivors “exhibited better short-term memory and shorter reaction time” compared to their wild-type controls, the researchers report in the journa.

According to the researchers, the experiments represent the first attempt to study the genetic basis of human brain origin using transgenic monkeys. The findings, they insist, “have the potential to provide important — and potentially unique — insights into basic questions of what actually makes humans unique.”

For others, the work provokes a profoundly moral and visceral uneasiness. Even one of the collaborators — University of North Carolina computer scientist Martin Styner — told MIT Technology Review he considered removing his name from the paper, which he said was unable to find a publisher in the West.

“Now we have created this animal which is different than it is supposed to be,” Styner said. “When we do experiments, we have to have a good understanding of what we are trying to learn, to help society, and that is not the case here.” l

In an email to the National Post, Styner said he has an expertise in medical image analysis and was approached by the researchers back in 2011. He said he had no input on the science in the project, beyond how to best do the analysis of their MRI data. “At the time, I did not think deeply enough about the ethical consideration.”

….

When it comes to the scientific use of nonhuman primates, ethicists say the moral compass is skewed in cases like this.

Given the kind of beings monkeys are, “I certainly would have thought you would have had to have a reasonable expectation of high benefit to human beings to justify the harms that you are going to have for intensely social, cognitively complex, emotional animals like monkeys,” said Letitia Meynell, an associate professor in the department of philosophy at Dalhousie University in Halifax.

“It’s not clear that this kind of research has any reasonable expectation of having any useful application for human beings,” she said.

The science itself is also highly dubious and fundamentally flawed in its logic, she said.
“If you took Einstein as a baby and you raised him in the lab he wouldn’t turn out to be Einstein,” Meynell said. “If you’re actually interested in studying the cognitive complexity of these animals, you’re not going to get a good representation of that by raising them in labs, because they can’t develop the kind of cognitive and social skills they would in their normal environment.”

The Chinese said the MCPH1 gene is one of the strongest candidates for human brain evolution. But looking at a single gene is just bad genetics, Meynell said. Multiple genes and their interactions affect the vast majority of traits.

My point is that there’s a lot of research focused on intelligence and genes when we don’t really know what role genes actually play and when there doesn’t seem to be any serious oversight.

Global plea for moratorium on heritable genome editing

A March 13, 2019 University of Otago (New Zealand) press release (also on EurekAlert) describes a global plea for a moratorium,

A University of Otago bioethicist has added his voice to a global plea for a moratorium on heritable genome editing from a group of international scientists and ethicists in the wake of the recent Chinese experiment aiming to produce HIV immune children.

In an article in the latest issue of international scientific journal Nature, Professor Jing-Bao Nie together with another 16 [17] academics from seven countries, call for a global moratorium on all clinical uses of human germline editing to make genetically modified children.

They would like an international governance framework – in which nations voluntarily commit to not approve any use of clinical germline editing unless certain conditions are met – to be created potentially for a five-year period.

Professor Nie says the scientific scandal of the experiment that led to the world’s first genetically modified babies raises many intriguing ethical, social and transcultural/transglobal issues. His main personal concerns include what he describes as the “inadequacy” of the Chinese and international responses to the experiment.

“The Chinese authorities have conducted a preliminary investigation into the scientist’s genetic misadventure and issued a draft new regulation on the related biotechnologies. These are welcome moves. Yet, by putting blame completely on the rogue scientist individually, the institutional failings are overlooked,” Professor Nie explains.

“In the international discourse, partly due to the mentality of dichotomising China and the West, a tendency exists to characterise the scandal as just a Chinese problem. As a result, the global context of the experiment and Chinese science schemes have been far from sufficiently examined.”

The group of 17 [18] scientists and bioethicists say it is imperative that extensive public discussions about the technical, scientific, medical, societal, ethical and moral issues must be considered before germline editing is permitted. A moratorium would provide time to establish broad societal consensus and an international framework.

“For germline editing to even be considered for a clinical application, its safety and efficacy must be sufficient – taking into account the unmet medical need, the risks and potential benefits and the existence of alternative approaches,” the opinion article states.

Although techniques have improved in recent years, germline editing is not yet safe or effective enough to justify any use in the clinic with the risk of failing to make the desired change or of introducing unintended mutations still unacceptably high, the scientists and ethicists say.

“No clinical application of germline editing should be considered unless its long-term biological consequences are sufficiently understood – both for individuals and for the human species.”

The proposed moratorium does not however, apply to germline editing for research uses or in human somatic (non-reproductive) cells to treat diseases.

Professor Nie considers it significant that current presidents of the UK Royal Society, the US National Academy of Medicine and the Director and Associate Director of the US National Institute of Health have expressed their strong support for such a proposed global moratorium in two correspondences published in the same issue of Nature. The editorial in the issue also argues that the right decision can be reached “only through engaging more communities in the debate”.

“The most challenging questions are whether international organisations and different countries will adopt a moratorium and if yes, whether it will be effective at all,” Professor Nie says.

A March 14, 2019 news item on phys.org provides a précis of the Comment in Nature. Or, you ,can access the Comment with this link

Adopt a moratorium on heritable genome editing; Eric Lander, Françoise Baylis, Feng Zhang, Emmanuelle Charpentier, Paul Berg and specialists from seven countries call for an international governance framework.signed by: Eric S. Lander, Françoise Baylis, Feng Zhang, Emmanuelle Charpentier, Paul Berg, Catherine Bourgain, Bärbel Friedrich, J. Keith Joung, Jinsong Li, David Liu, Luigi Naldini, Jing-Bao Nie, Renzong Qiu, Bettina Schoene-Seifert, Feng Shao, Sharon Terry, Wensheng Wei, & Ernst-Ludwig Winnacker. Nature 567, 165-168 (2019) doi: 10.1038/d41586-019-00726-5

This Comment in Nature is open access.

World Health Organization (WHO) chimes in

Better late than never, eh? The World Health Organization has called heritable gene editing of humans ‘irresponsible’ and made recommendations. From a March 19, 2019 news item on the Canadian Broadcasting Corporation’s Online news webpage,

A panel convened by the World Health Organization said it would be “irresponsible” for scientists to use gene editing for reproductive purposes, but stopped short of calling for a ban.

The experts also called for the U.N. health agency to create a database of scientists working on gene editing. The recommendation was announced Tuesday after a two-day meeting in Geneva to examine the scientific, ethical, social and legal challenges of such research.

“At this time, it is irresponsible for anyone to proceed” with making gene-edited babies since DNA changes could be passed down to future generations, the experts said in a statement.

Germline editing has been on my radar since 2015 (see my May 14, 2015 posting) and the probability that someone would experiment with viable embryos and bring them to term shouldn’t be that much of a surprise.

Slow science from Canada

Canada has banned germline editing but there is pressure to lift that ban. (I touched on the specifics of the campaign in an April 26, 2019 posting.) This March 17, 2019 essay on The Conversation by Landon J Getz and Graham Dellaire, both of Dalhousie University (Nova Scotia, Canada) elucidates some of the discussion about whether research into germline editing should be slowed down.

Naughty (or Haughty, if you prefer) scientists

There was scoffing from some, if not all, members of the scientific community about the potential for ‘designer babies’ that can be seen in an excerpt from an article by Ed Yong for The Atlantic (originally published in my ,August 15, 2017 posting titled: CRISPR and editing the germline in the US (part 2 of 3): ‘designer babies’?),

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

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

Then about 15 months later, the possibility seemed to be realized.

Interesting that scientists scoffed at the public’s concerns (you can find similar arguments about robots and artificial intelligence not being a potentially catastrophic problem), yes? Often, nonscientists’ concerns are dismissed as being founded in science fiction.

To be fair, there are times when concerns are overblown, the difficulty is that it seems the scientific community’s default position is to uniformly dismiss concerns rather than approaching them in a nuanced fashion. If the scoffers had taken the time to think about it, germline editing on viable embryos seems like an obvious and inevitable next step (as I’ve noted previously).

At this point, no one seems to know if He actually succeeded at removing CCR5 from Lulu’s and Nana’s genomes. In November 2018, scientists were guessing that at least one of the twins was a ‘mosaic’. In other words, some of her cells did not include CCR5 while others did.

Parents, children, competition

A recent college admissions scandal in the US has highlighted the intense competition to get into high profile educational institutions. (This scandal brought to mind the Silicon Valey elite who wanted to know more about gene editing that might result in improved cognitive skills.)

Since it can be easy to point the finger at people in other countries, I’d like to note that there was a Canadian parent among these wealthy US parents attempting to give their children advantages by any means, legal or not. (Note: These are alleged illegalities.) From a March 12, 2019 news article by Scott Brown, Kevin Griffin, and Keith Fraser for the Vancouver Sun,

Vancouver businessman and former CFL [Canadian Football League] player David Sidoo has been charged with conspiracy to commit mail and wire fraud in connection with a far-reaching FBI investigation into a criminal conspiracy that sought to help privileged kids with middling grades gain admission to elite U.S. universities.

In a 12-page indictment filed March 5 [2019] in the U.S. District Court of Massachusetts, Sidoo is accused of making two separate US$100,000 payments to have others take college entrance exams in place of his two sons.

Sidoo is also accused of providing documents for the purpose of creating falsified identification cards for the people taking the tests.

In what is being called the biggest college-admissions scam ever prosecuted by the U.S. Justice Department, Sidoo has been charged with nearly 50 other people. Nine athletic coaches and 33 parents including Hollywood actresses Felicity Huffman and Lori Loughlin. are among those charged in the investigation, dubbed Operation Varsity Blues.

According to the indictment, an unidentified person flew from Tampa, Fla., to Vancouver in 2011 to take the Scholastic Aptitude Test (SAT) in place of Sidoo’s older son and was directed not to obtain too high a score since the older son had previously taken the exam, obtaining a score of 1460 out of a possible 2400.

A copy of the resulting SAT score — 1670 out of 2400 — was mailed to Chapman University, a private university in Orange, Calif., on behalf of the older son, who was admitted to and ultimately enrolled in the university in January 2012, according to the indictment.

It’s also alleged that Sidoo arranged to have someone secretly take the older boy’s Canadian high school graduation exam, with the person posing as the boy taking the exam in June 2012.

The Vancouver businessman is also alleged to have paid another $100,000 to have someone take the SAT in place of his younger son.

Sidoo, an investment banker currently serving as CEO of Advantage Lithium, was awarded the Order of B.C. in 2016 for his philanthropic efforts.

He is a former star with the UBC [University of British Columbia] Thunderbirds football team and helped the school win its first Vanier Cup in 1982. He went on to play five seasons in the CFL with the Saskatchewan Roughriders and B.C. Lions.

Sidoo is a prominent donor to UBC and is credited with spearheading an alumni fundraising campaign, 13th Man Foundation, that resuscitated the school’s once struggling football team. He reportedly donated $2 million of his own money to support the program.

Sidoo Field at UBC’s Thunderbird Stadium is named in his honour.

In 2016, he received the B.C. [British Columbia] Sports Hall of Fame’s W.A.C. Bennett Award for his contributions to the sporting life of the province.

The question of whether or not these people like the ‘Silicon Valley elite’ (mentioned in John Loeffler’s February 22, 2019 article) would choose to tinker with their children’s genome if it gave them an advantage, is still hypothetical but it’s easy to believe that at least some might seriously consider the possibility especially if the researcher or doctor didn’t fully explain just how little is known about the impact of tinkering with the genome. For example, there’s a big question about whether those parents in China fully understood what they signed up for.

By the way, cheating scandals aren’t new (see Vanity Fair’s Schools For Scandal; The Inside Dramas at 16 of America’s Most Elite Campuses—Plus Oxford! Edited by Graydon Carter, published in August 2018 and covering 25 years of the magazine’s reporting). On a similar line, there’s this March13, 2019 essay which picks apart some of the hierarchical and power issues at play in the US higher educational system which led to this latest (but likely not last) scandal.

Scientists under pressure

While Kofler’s February 26, 2019 Nature opinion piece and call to action seems to address the concerns regarding germline editing by advocating that scientists become more conscious of how their choices impact society, as I noted earlier, the ideas expressed seem a little ungrounded in harsh realities. Perhaps it’s time to give some recognition to the various pressures put on scientists from their own governments and from an academic environment that fosters ‘success’ at any cost to peer pressure, etc. (For more about the costs of a science culture focused on success, read this March 2, 2019 blog posting by Jon Tennant on digital-science.com for a breakdown.)

One other thing I should mention, for some scientists getting into the history books, winning Nobel prizes, etc. is a very important goal. Scientists are people too.

Some thoughts

There seems to be a great disjunction between what Richardson presents as an alternative narrative to the ‘gene-god’ and how genetic research is being performed and reported on. What is clear to me is that no one really understands genetics and this business of inserting and deleting genes is essentially research designed to satisfy curiosity and/or allay fears about being left behind in a great scientific race to a an unknown destination.

I’d like to see some better reporting and a more agile response by the scientific community, the various governments, and international agencies. What shape or form a more agile response might take, I don’t know but I’d like to see some efforts.

Back to the regular programme

There’s a lot about CRISPR here on this blog. A simple search of ‘CRISPR ‘in the blog’s search engine should get you more than enough information about the technology and the various issues ranging from intellectual property to risks and more.

The three part series (CRISPR and editing the germline in the US …), mentioned previously, was occasioned by the publication of a study on germline editing research with nonviable embryos in the US. The 2017 research was done at the Oregon Health and Science University by Shoukhrat Mitalipov following similar research published by Chinese scientists in 2015. The series gives relatively complete coverage of the issues along with an introduction to CRISPR and embedded video describing the technique. Here’s part 1 to get you started..

How do nanoparticles interact with the environment and with humans over time?

I meant to get this piece published sooner but good intentions don’t get you far.

At Northwestern University, scientists have researched the impact engineered nanoparticles (ENPs) might have as they enter the food chain. An October 18, 2019 Northwestern University news release (also on EurekAlert) by Megan Fellman describes research on an investigation of ENPs and their interaction with living organisms,

Personal electronic devices — smartphones, computers, TVs, tablets, screens of all kinds — are a significant and growing source of the world’s electronic waste. Many of these products use nanomaterials, but little is known about how these modern materials and their tiny particles interact with the environment and living things.

Now a research team of Northwestern University chemists and colleagues from the national Center for Sustainable Nanotechnology has discovered that when certain coated nanoparticles interact with living organisms it results in new properties that cause the nanoparticles to become sticky. Fragmented lipid coronas form on the particles, causing them to stick together and grow into long kelp-like strands. Nanoparticles with 5-nanometer diameters form long structures that are microns in size in solution. The impact on cells is not known.

“Why not make a particle that is benign from the beginning?” said Franz M. Geiger, professor of chemistry in Northwestern’s Weinberg College of Arts and Sciences. He led the Northwestern portion of the research.

“This study provides insight into the molecular mechanisms by which nanoparticles interact with biological systems,” Geiger said. “This may help us understand and predict why some nanomaterial/ligand coating combinations are detrimental to cellular organisms while others are not. We can use this to engineer nanoparticles that are benign by design.”

Using experiments and computer simulations, the research team studied how gold nanoparticles wrapped in strings having positively charged beads interact with a variety of bilayer membrane models. The researchers found that a nearly circular layer of lipids forms spontaneously around the particles. Formation of these “fragmented lipid coronas” have never been seen before to form from membranes.

The study points to solving problems with chemistry. Scientists can use the findings to design a better ligand coating for nanoparticles that avoids the ammonium-phosphate interaction, which causes the aggregation. (Ligands are used in nanomaterials for layering.)

The results will be published Oct. 18 [2018] in the journal Chem.

Geiger is the study’s corresponding author. Other authors include scientists from the Center for Sustainable Nanotechnology’s other institutional partners. Based at the University of Wisconsin-Madison, the center studies engineered nanomaterials and their interaction with the environment, including biological systems — both the negative and positive aspects.

“The nanoparticles pick up parts of the lipid cellular membrane like a snowball rolling in a snowfield, and they become sticky,” Geiger said. “This unintended effect happens because of the presence of the nanoparticle. It can bring lipids to places in cells where lipids are not meant to be.”

The experiments were conducted in idealized laboratory settings that nevertheless are relevant to environments found during the late summer in a landfill — at 21-22 degrees Celsius and a couple feet below ground, where soil and groundwater mix and the food chain begins.

By pairing spectroscopic and imaging experiments with atomistic and coarse-grain simulations, the researchers identified that ion pairing between the lipid head groups of biological membranes and the polycations’ ammonium groups in the nanoparticle wrapping leads to the formation of fragmented lipid coronas. These coronas engender new properties, including composition and stickiness, to the particles with diameters below 10 nanometers.

The study’s insights help predict the impact that the increasingly widespread use of engineered nanomaterials has on the nanoparticles’ fate once they enter the food chain, which many of them may eventually do.

“New technologies and mass consumer products are emerging that feature nanomaterials as critical operational components,” Geiger said. “We can upend the existing paradigm in nanomaterial production towards one in which companies design nanomaterials to be sustainable from the beginning, as opposed to risking expensive product recalls — or worse — down the road.” [emphases mine]

Here’s an image illustrating the work,

Caption: This is a computer simulation of a lipid corona around a 5-nanometer nanoparticle showing ammonium-phosphate ion pairing. Credit: Northwestern University

The curious can find the paper here,

Lipid Corona Formation from Nanoparticle Interactions with Bilayers by Laura L. Olenick, Julianne M. Troiano, Ariane Vartanian, Eric S. Melby, Arielle C. Mensch, Leili Zhang, Jiewei Hong, Oluwaseun Mesele, Tian Qiu, Jared Bozich, Samuel Lohse, Xi Zhang, Thomas R. Kuech, Augusto Millevolte, Ian Gunsolus, Alicia C. McGeachy, Merve Doğangün, Tianzhe Li, Dehong Hu, Stephanie R. Walter, Aurash Mohaimani, Angela Schmoldt, Marco D. Torelli, Katherine R. Hurley, Joe Dalluge, Gene Chong, Z. Vivian Feng, Christy L. Haynes, Robert J. Hamers, Joel A. Pedersen, Qiang Cui, Rigoberto Hernandez, Rebecca Klaper, Galya Orr, Catherine J. Murphy, Franz M. Geiger. Chem Volume 4, ISSUE 11, P2709-2723, November 08, 2018 DOI:https://doi.org/10.1016/j.chempr.2018.09.018 Published:October 18, 2018

This paper is behind a paywall.

Snakebite? Roll out the nanoparticles

An October 4, 2018 news item on Nanowerk highlights some recent research into treating snakebites (Note: A link has been removed),

Venomous snakebites affect 2.5 million people, and annually cause more than 100,000 deaths and leave 400,000 individuals with permanent physical and psychological trauma each year.

Researchers reporting in PLOS Neglected Tropical Diseases (“Engineered nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis”) have now described a new approach to treating snake bites [sic], using nanoparticles to bind to venom toxins and prevent the spread of venom through the body.

Caption: “Synthetic polymer nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis.” Credit: Shea, et al. CC BY 4.0: Redistribution allowed with credit

An October 4, 2018 PLOS news release on EurekAlert, which originated the news item, expands on the theme,

The standard treatment for snakebites is the intravenous administration of IgG immune molecules that recognize venoms. However, such antivenom therapies must be administered quickly–and by trained healthcare workers– to be effective and are highly specific to particular venoms. There is an ongoing need for a snakebite treatment which can be used in a rural setting and works against the bites of diverse venomous snakes.

In the new work, Kenneth Shea, of the University of California, Irvine, and colleagues engineered nanoparticles that bind to and sequester an array of phospholipases A2 (PLA2) and three-finger toxin (3FTX) molecules found in Elapidae snake venoms. The Elapidae family is a large family of venomous snakes that includes cobras, kraits, tiger snakes, sea snakes, coral snakes and mambas, among other species. The researchers tested the ability of the nanoparticles to block Naja nigricollis (black-necked spitting cobra) venom in mice that received varying doses of the nanoparticles, injected into the skin. Envenomings by this snake in sub-Saharan Africa inflict serious cutaneous necrosis that may leave permanent tissue damage in the victims.

In experiments on isolated cells, the nanoparticles were found to sequester a wide range of Elapidae PLA and 3FTX venoms. Moreover, with collaborator José María Gutiérrez from the Instituto Clodomiro Picado (Universidad de Costa Rica), experiments with mice demonstrated that injections of the nanoparticles at the site of venom injection significantly mitigated the typical necrotic effects–including blistering and ulcers– of the spitting cobra venom. The nanoparticles administered to mice that had not received venom did not have an effect on skin and did not induce systemic toxicity.

“The stable, low-cost nanoparticles have the potential to be administered subcutaneously immediately after the bite at the site of envenoming by this spitting cobra to halt or reduce the extent of local damage and mitigate the systemic distribution of toxins post-envenoming,” the researchers say.

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

Engineered nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis by Jeffrey O’Brien, Shih-Hui Lee, José María Gutiérrez, Kenneth J. Shea. PLOS Neglected Tropical Diseases 12(10): e0006736 DOI: https://doi.org/10.1371/journal.pntd.0006736 Published: October 4, 2018

This paper is open access. By the way, PLOS stands for Public Library of Science.

Real-time tracking of UV (ultraviolet light) exposure for all skin types (light to dark)

It’s nice to find this research after my August 21, 2018 posting where I highlighted (scroll down to ‘Final comments’) the issues around databases and skin cancer data which is usually derived from fair-skinned people while people with darker hues tend not to be included. This is partly due to the fact that fair-skinned people have a higher risk and also partly due to myths about how more melanin in your skin somehow protects you from skin cancer.

This October 4, 2018 news item on ScienceDaily announces research into a way to track UV exposure for all skin types,

Researchers from the University of Granada [Spain] and RMIT University in Melbourne [Australia] have developed personalised and low-cost wearable ultraviolet (UV) sensors that warn users when their exposure to the sun has become dangerous.

The paper-based sensor, which can be worn as a wristband, features happy and sad emoticon faces — drawn in an invisible UV-sensitive ink — that successively light up as you reach 25%, 50%, 75% and finally 100% of your daily recommended UV exposure.

The research team have also created six versions of the colour-changing wristbands, each of which is personalised for a specific skin tone  [emphasis mine]– an important characteristic given that darker people need more sun exposure to produce vitamin D, which is essential for healthy bones, teeth and muscles.

An October 2, 2018 University of Granada press release (also on EurekAlert) delves further,

Four of the wristbands, each of which indicates a different stage of exposure to UV radiation (25%, 50%, 75% and 100%)

The emoticon faces on the wristband successively “light up” as exposure to UV radiation increases

Skin cancer, one of the most common types of cancer throughout the world, is primarily caused by overexposure to ultraviolet radiation (UVR). In Spain, over 74,000 people are diagnosed with non-melanoma skin cancer every year, while a further 4,000 are diagnosed with melanoma skin cancer. In regions such as Australia, where the ozone layer has been substantially depleted, it is estimated that approximately 2 in 3 people will be diagnosed with skin cancer by the time they reach the age of 70.

“UVB and UVC radiation is retained by the ozone layer. This sensor is especially important in the current context, given that the hole in the ozone layer is exposing us to such dangerous radiation”, explains José Manuel Domínguez Vera, a researcher at the University of Granada’s Department of Inorganic Chemistry and the main author of the paper.

Domínguez Vera also highlights that other sensors currently available on the market only measure overall UV radiation, without distinguishing between UVA, UVB and UVC, each of which has a significantly different impact on human health.  In contrast, the new paper-based sensor can differentiate between UVA, UVB and UVC radiation. Prolonged exposure to UVA radiation is associated with skin ageing and wrinkling, while excessive exposure to UVB causes sunburn and increases the likelihood of skin cancer and eye damage.

Drawbacks of the traditional UV index

Ultraviolet radiation is determined by aspects such as location, time of day, pollution levels, astronomical factors, weather conditions such as clouds, and can be heightened by reflective surfaces like bodies of water, sand and snow. But UV rays are not visible to the human eye (even if it is cloudy UV radiation can be high) and until now the only way of monitoring UV intensity has been to use the UV index, which is standardly given in weather reports and indicates 5 degrees of radiation;  low, moderate, high, very high or extreme.

Despite its usefulness, the UV index is a relatively limited tool. For instance, it does not clearly indicate what time of the day or for how long you should be outside to get your essential vitamin D dose, or when to cover up to avoid sunburn and a heightened risk of skin cancer.

Moreover, the UV index is normally based on calculations for fair skin, making it unsuitable for ethnically diverse populations.  While individuals with fairer skin are more susceptible to UV damage, those with darker skin require much longer periods in the sun in order to absorb healthy amounts of vitamin D. In this regard, the UV index is not an accurate tool for gauging and monitoring an individual’s recommended daily exposure.

UV-sensitive ink

The research team set out to tackle the drawbacks of the traditional UV index by developing an inexpensive, disposable and personalised sensor that allows the wearer to track their UV exposure in real-time. The sensor paper they created features a special ink, containing phosphomolybdic acid (PMA), which turns from colourless to blue when exposed to UV radiation. They can use the initially-invisible ink to draw faces—or any other design—on paper and other surfaces. Depending on the type and intensity of the UV radiation to which the ink is exposed, the paper begins to turn blue; the greater the exposure to UV radiation, the faster the paper turns blue.

Additionally, by tweaking the ink composition and the sensor design, the team were able to make the ink change colour faster or slower, allowing them to produce different sensors that are tailored to the six different types of skin colour. [emphasis mine]

Applications beyond health

This low-cost, paper-based sensor technology will not only help people of all colours to strike an optimum balance between absorbing enough vitamin D and avoiding sun damage — it also has significant applications for the agricultural and industrial sectors. UV rays affect the growth of crops and the shelf life of a range of consumer products. As the UV sensors can detect even the slightest doses of UV radiation, as well as the most extreme, this new technology could have vast potential for industries and companies seeking to evaluate the prolonged impact of UV exposure on products that are cultivated or kept outdoors.

The research project is the result of fruitful collaborations between two members of the UGR BIONanoMet (FQM368) research group; Ana González and José Manuel Domínguez-Vera, and the research group led by Dr. Vipul Bansal at RMIT University in Melbourne (Australia).

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

Skin color-specific and spectrally-selective naked-eye dosimetry of UVA, B and C radiations by Wenyue Zou, Ana González, Deshetti Jampaiah, Rajesh Ramanathan, Mohammad Taha, Sumeet Walia, Sharath Sriram, Madhu Bhaskaran, José M. Dominguez-Vera, & Vipul Bansal. Nature Communicationsvolume 9, Article number: 3743 (2018) DOI: https://doi.org/10.1038/s41467-018-06273-3 Published 25 September 2018

This paper is open access.

Cannibalisitic nanostructures

I think this form of ‘cannibalism’ could also be described as a form of ‘self-assembly’. That said, here is an August 31, 2018 news item on ScienceDaily announcing ‘cannibalistic’ materials,

Scientists at the [US] Department of Energy’s [DOE] Oak Ridge National Laboratory [ORNL] induced a two-dimensional material to cannibalize itself for atomic “building blocks” from which stable structures formed.

The findings, reported in Nature Communications, provide insights that may improve design of 2D materials for fast-charging energy-storage and electronic devices.

An August 31, 2018 DOE/Oak Ridge National Laboratory news release (also on EurekAlert), which originated the news item, provides more detail (Note: Links have been removed),

“Under our experimental conditions, titanium and carbon atoms can spontaneously form an atomically thin layer of 2D transition-metal carbide, which was never observed before,” said Xiahan Sang of ORNL.

He and ORNL’s Raymond Unocic led a team that performed in situ experiments using state-of-the-art scanning transmission electron microscopy (STEM), combined with theory-based simulations, to reveal the mechanism’s atomistic details.

“This study is about determining the atomic-level mechanisms and kinetics that are responsible for forming new structures of a 2D transition-metal carbide such that new synthesis methods can be realized for this class of materials,” Unocic added.

The starting material was a 2D ceramic called a MXene (pronounced “max een”). Unlike most ceramics, MXenes are good electrical conductors because they are made from alternating atomic layers of carbon or nitrogen sandwiched within transition metals like titanium.

The research was a project of the Fluid Interface Reactions, Structures and Transport (FIRST) Center, a DOE Energy Frontier Research Center that explores fluid–solid interface reactions that have consequences for energy transport in everyday applications. Scientists conducted experiments to synthesize and characterize advanced materials and performed theory and simulation work to explain observed structural and functional properties of the materials. New knowledge from FIRST projects provides guideposts for future studies.

The high-quality material used in these experiments was synthesized by Drexel University scientists, in the form of five-ply single-crystal monolayer flakes of MXene. The flakes were taken from a parent crystal called “MAX,” which contains a transition metal denoted by “M”; an element such as aluminum or silicon, denoted by “A”; and either a carbon or nitrogen atom, denoted by “X.” The researchers used an acidic solution to etch out the monoatomic aluminum layers, exfoliate the material and delaminate it into individual monolayers of a titanium carbide MXene (Ti3C2).

The ORNL scientists suspended a large MXene flake on a heating chip with holes drilled in it so no support material, or substrate, interfered with the flake. Under vacuum, the suspended flake was exposed to heat and irradiated with an electron beam to clean the MXene surface and fully expose the layer of titanium atoms.

MXenes are typically inert because their surfaces are covered with protective functional groups—oxygen, hydrogen and fluorine atoms that remain after acid exfoliation. After protective groups are removed, the remaining material activates. Atomic-scale defects—“vacancies” created when titanium atoms are removed during etching—are exposed on the outer ply of the monolayer. “These atomic vacancies are good initiation sites,” Sang said. “It’s favorable for titanium and carbon atoms to move from defective sites to the surface.” In an area with a defect, a pore may form when atoms migrate.

“Once those functional groups are gone, now you’re left with a bare titanium layer (and underneath, alternating carbon, titanium, carbon, titanium) that’s free to reconstruct and form new structures on top of existing structures,” Sang said.

High-resolution STEM imaging proved that atoms moved from one part of the material to another to build structures. Because the material feeds on itself, the growth mechanism is cannibalistic.

“The growth mechanism is completely supported by density functional theory and reactive molecular dynamics simulations, thus opening up future possibilities to use these theory tools to determine the experimental parameters required for synthesizing specific defect structures,” said Adri van Duin of Penn State [Pennsylvania State University].

Most of the time, only one additional layer [of carbon and titanium] grew on a surface. The material changed as atoms built new layers. Ti3C2 turned into Ti4C3, for example.

“These materials are efficient at ionic transport, which lends itself well to battery and supercapacitor applications,” Unocic said. “How does ionic transport change when we add more layers to nanometer-thin MXene sheets?” This question may spur future studies.

“Because MXenes containing molybdenum, niobium, vanadium, tantalum, hafnium, chromium and other metals are available, there are opportunities to make a variety of new structures containing more than three or four metal atoms in cross-section (the current limit for MXenes produced from MAX phases),” Yury Gogotsi of Drexel University added. “Those materials may show different useful properties and create an array of 2D building blocks for advancing technology.”

At ORNL’s Center for Nanophase Materials Sciences (CNMS), Yu Xie, Weiwei Sun and Paul Kent performed first-principles theory calculations to explain why these materials grew layer by layer instead of forming alternate structures, such as squares. Xufan Li and Kai Xiao helped understand the growth mechanism, which minimizes surface energy to stabilize atomic configurations. Penn State scientists conducted large-scale dynamical reactive force field simulations showing how atoms rearranged on surfaces, confirming defect structures and their evolution as observed in experiments.

The researchers hope the new knowledge will help others grow advanced materials and generate useful nanoscale structures.

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

In situ atomistic insight into the growth mechanisms of single layer 2D transition metal carbides by Xiahan Sang, Yu Xie, Dundar E. Yilmaz, Roghayyeh Lotfi, Mohamed Alhabeb, Alireza Ostadhossein, Babak Anasori, Weiwei Sun, Xufan Li, Kai Xiao, Paul R. C. Kent, Adri C. T. van Duin, Yury Gogotsi, & Raymond R. Unocic. Nature Communicationsvolume 9, Article number: 2266 (2018) DOI: https://doi.org/10.1038/s41467-018-04610-0 Published 11 June 2018

This paper is open access.

Where do I stand? a graphene artwork

A May 2,2019 news item on Nanowerk describes some graphene-based artwork being created at Rice University (Texas, US), Note: A link has been removed,

When you read about electrifying art, “electrifying” isn’t usually a verb. But an artist working with a Rice University lab is in fact making artwork that can deliver a jolt.

The Rice lab of chemist James Tour introduced laser-induced graphene (LIG) to the world in 2014, and now the researchers are making art with the technique, which involves converting carbon in a common polymer or other material into microscopic flakes of graphene.

The “ink” in “Where Do I Stand?” by artist Joseph Cohen is actually laser-induced graphene (LIG). The design shows Cohen’s impression of what LIG looks like at the microscopic level. The work was produced in the Rice University lab where the technique of creating LIG was invented. Photo by Jeff Fitlow
A detail from “Where Do I Stand?” by artist Joseph Cohen, who created the work at Rice University using laser-induced graphene as the medium. Photo by Jeff Fitlow

A May 2, 2019 Rice university news release (also received via email), which originated the news item, describes laser-induced graphene (LIG) and the art in more detail (Note: Links have been removed),

LIG is metallic and conducts electricity. The interconnected flakes are effectively a wire that could empower electronic artworks.

The paper in the American Chemical Society journal ACS Applied Nano Materials – simply titled “Graphene Art” – lays out how the lab and Houston artist and co-author Joseph Cohen generated LIG portraits and prints, including a graphene-inspired landscape called “Where Do I Stand?”

While the work isn’t electrified, Cohen said it lays the groundwork for future possibilities.

“That’s what I would like to do,” he said. “Not make it kitsch or play off the novelty, but to have it have some true functionality that allows greater awareness about the material and opens up the experience.”

Cohen created the design in an illustration program and sent it directly to the industrial engraving laser Tour’s lab uses to create LIG on a variety of materials. The laser burned the artist’s fine lines into the substrate, in this case archive-quality paper treated with fire retardant.

The piece, which was part of Cohen’s exhibit at Rice’s BioScience Research Collaborative last year, peers into the depths of what a viewer shrunken to nanoscale might see when facing a field of LIG, with overlapping hexagons – the basic lattice of atom-thick graphene – disappearing into the distance.

“You’re looking at this image of a 3D foam matrix of laser-induced graphene and it’s actually made of LIG,” he said. “I didn’t base it on anything; I was just thinking about what it would look like. When I shared it with Jim, he said, ‘Wow, that’s what it would look like if you could really blow this up.’”

Cohen said his art is about media specificity.

“In terms of the artistic application, you’re not looking at a representation of something, as traditionally we would in the history of art,” he said. “Each piece is 100% original. That’s the key.”

He developed an interest in nanomaterials as media for his art when he began work with Rice alumnus Daniel Heller, a bioengineer at Memorial Sloan Kettering Cancer Center in New York who established an artist-in-residency position in his lab.

After two years of creating with carbon nanotube-infused paint, Cohen attended an Electrochemical Society conference and met Tour, who in turn introduced him to Rice chemists Bruce Weisman and Paul Cherukuri, who further inspired his investigation of nanotechnology.

The rest is art history.

It would be incorrect to think of the process as “printing,” Tour said. Instead of adding a substance to the treated paper, substance is burned away as the laser turns the surface into foamlike flakes of interconnected graphene.

The art itself can be much more than eye candy, given LIG’s potential for electronic applications like sensors or as triboelectric generators that turn mechanical actions into current.

“You could put LIG on your back and have it flash LEDs with every step you take,” Tour said.

The fact that graphene is a conductor — unlike paint, ink or graphite from a pencil — makes it particularly appealing to Cohen, who expects to take advantage of that capability in future works.

“It’s art with a capital A that is trying to do the most that it can with advancements in science and technology,” he said. “If we look back historically, from the Renaissance to today, the highest forms of art push the limits of human understanding.”

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

Graphene Art by Yieu Chyan, Joseph Cohen, Winston Wang, Chenhao Zhang, and James M. Tour. ACS Appl. Nano Mater., Article ASAP DOI: 10.1021/acsanm.9b00391 Publication Date (Web): April 23, 2019

Copyright © 2019 American Chemical Society

This paper appears to be open access.

Because I can’t resist the delight beaming from these faces,

maging with laser-induced graphene (LIG) was taken to a new level in a Rice University lab. From left, chemist James Tour, holding a portrait of himself in LIG; artist Joseph Cohen, holding his work “Where Do I Stand?”; and Yieu Chyan, a Rice graduate student and lead author of a new paper detailing the process used to create the art. Photo by Jeff Fitlow

I am a sound speaker/loudspeaker (well, maybe one day)

Caption: From left are Saewon Kang, Professor Hyunhyub Ko, and Seungse Cho in the School of Energy and Chemical Engineering at UNIST. Credit: UNIST

What are these scientists so happy about? A September 18, 2018 news item on ScienceDaily reveals all,

An international team of researchers, affiliated with UNIST [Ulsan National Institute of Science and Technology] has presented an innovative wearable technology that will turn your skin into a loudspeaker.

An August 6, 2018 UNIST press release (also on EurekAlert but published September 17,2018), which originated the news item, delves further into the research,

This breakthrough has been led by Professor Hyunhyub Ko in the School of Energy and Chemical Engineering at UNIST. Created in part to help the hearing and speech impaired, the new technology can be further explored for various potential applications, such as wearable IoT sensors and conformal health care devices.

In the study, the research team has developed ultrathin, transparent, and conductive hybrid nanomembranes with nanoscale thickness, consisting of an orthogonal silver nanowire array embedded in a polymer matrix. They, then, demonstrated their nanomembrane by making it into a loudspeaker that can be attached to almost anything to produce sounds. The researchers also introduced a similar device, acting as a microphone, which can be connected to smartphones and computers to unlock voice-activated security systems.

Nanomembranes (NMs) are molcularly thin seperation layers with nanoscale thickness. Polymer NMs have attracted considerable attention owing to their outstanding advantages, such as extreme flexibility, ultralight weight, and excellent adhesibility in that they can be attached directly to almost any surface. However, they tear easily and exhibit no electrical conductivity.

The research team has solved such issues by embedding a silver nanowire network within a polymer-based nanomembrane. This has enabled the demonstration of skin-attachable and imperceptible loudspeaker and microphone.

“Our ultrathin, transparent, and conductive hybrid NMs facilitate conformal contact with curvilinear and dynamic surfaces without any cracking or rupture,” says  Saewon Kang in the doctroral program of Energy and Chemical Engineering at UNIST, the first author of the study.

He adds, “These layers are capable of detecting sounds and vocal vibrations produced by the triboelectric voltage signals corresponding to sounds, which could be further explored for various potential applications, such as sound input/output devices.”

Using the hybrid NMs, the research team fabricated skin-attachable NM loudspeakers and microphones, which would be unobtrusive in appearance because of their excellent transparency and conformal contact capability. These wearable speakers and microphones are paper-thin, yet still capable of conducting sound signals.

“The biggest breakthrough of our research is the development of ultrathin, transparent, and conductive hybrid nanomembranes with nanoscale thickness, less than 100 nanometers,” says Professor Ko. “These outstanding optical, electrical, and mechanical properties of nanomembranes enable the demonstration of skin-attachable and imperceptible loudspeaker and microphone.”The skin-attachable NM loudspeakers work by emitting thermoacoustic sound by the temperature-induced oscillation of the surrounding air. The periodic Joule heating that occurs when an electric current passes through a conductor and produces heat leads to these temperature oscillations. It has attracted considerable attention for being a stretchable, transparent, and skin-attachable loudspeaker.

Wearable microphones are sensors, attached to a speaker’s neck to even sense the vibration of the vocal folds. This sensor operates by converting the frictional force generated by the oscillation of the transparent conductive nanofiber into electric energy. For the operation of the microphone, the hybrid nanomembrane is inserted between elastic films with tiny patterns to precisely detect the sound and the vibration of the vocal cords based on a triboelectric voltage that results from the contact with the elastic films.

“For the commercial applications, the mechanical durability of nanomebranes and the performance of loudspeaker and microphone should be improved further,” says Professor Ko.

Thankfully, the researchers have made video that lets us hear this sound speaker,


Paper-thin stick-on speakers, developed by Professor Hyunhyub Ko and his research team at UNIST.

Thank you to the folks at UNIST for including something with the sound. Strangely, it’s not common practice to include audio when publishing research on sound, not in my experience anyway..

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

Transparent and conductive nanomembranes with orthogonal silver nanowire arrays for skin-attachable loudspeakers and microphones by Saewon Kang, Seungse Cho, Ravi Shanker, Hochan Lee, Jonghwa Park, Doo-Seung Um, Youngoh Lee, and Hyunhyub Ko. Science Advances 03 Aug 2018: Vol. 4, no. 8, eaas8772 DOI: 10.1126/sciadv.aas8772

This paper appears to be open access.

Gene editing and personalized medicine: Canada

Back in the fall of 2018 I came across one of those overexcited pieces about personalized medicine and gene editing tha are out there. This one came from an unexpected source, an author who is a “PhD Scientist in Medical Science (Blood and Vasculature” (from Rick Gierczak’s LinkedIn profile).

It starts our promisingly enough although I’m beginning to dread the use of the word ‘precise’  where medicine is concerned, (from a September 17, 2018 posting on the Science Borealis blog by Rick Gierczak (Note: Links have been removed),

CRISPR-Cas9 technology was accidentally discovered in the 1980s when scientists were researching how bacteria defend themselves against viral infection. While studying bacterial DNA called clustered regularly interspaced short palindromic repeats (CRISPR), they identified additional CRISPR-associated (Cas) protein molecules. Together, CRISPR and one of those protein molecules, termed Cas9, can locate and cut precise regions of bacterial DNA. By 2012, researchers understood that the technology could be modified and used more generally to edit the DNA of any plant or animal. In 2015, the American Association for the Advancement of Science chose CRISPR-Cas9 as science’s “Breakthrough of the Year”.

Today, CRISPR-Cas9 is a powerful and precise gene-editing tool [emphasis mine] made of two molecules: a protein that cuts DNA (Cas9) and a custom-made length of RNA that works like a GPS for locating the exact spot that needs to be edited (CRISPR). Once inside the target cell nucleus, these two molecules begin editing the DNA. After the desired changes are made, they use a repair mechanism to stitch the new DNA into place. Cas9 never changes, but the CRISPR molecule must be tailored for each new target — a relatively easy process in the lab. However, it’s not perfect, and occasionally the wrong DNA is altered [emphasis mine].

Note that Gierczak makes a point of mentioning that CRISPR/Cas9 is “not perfect.” And then, he gets excited (Note: Links have been removed),

CRISPR-Cas9 has the potential to treat serious human diseases, many of which are caused by a single “letter” mutation in the genetic code (A, C, T, or G) that could be corrected by precise editing. [emphasis mine] Some companies are taking notice of the technology. A case in point is CRISPR Therapeutics, which recently developed a treatment for sickle cell disease, a blood disorder that causes a decrease in oxygen transport in the body. The therapy targets a special gene called fetal hemoglobin that’s switched off a few months after birth. Treatment involves removing stem cells from the patient’s bone marrow and editing the gene to turn it back on using CRISPR-Cas9. These new stem cells are returned to the patient ready to produce normal red blood cells. In this case, the risk of error is eliminated because the new cells are screened for the correct edit before use.

The breakthroughs shown by companies like CRISPR Therapeutics are evidence that personalized medicine has arrived. [emphasis mine] However, these discoveries will require government regulatory approval from the countries where the treatment is going to be used. In the US, the Food and Drug Administration (FDA) has developed new regulations allowing somatic (i.e., non-germ) cell editing and clinical trials to proceed. [emphasis mine]

The potential treatment for sickle cell disease is exciting but Gierczak offers no evidence that this treatment or any unnamed others constitute proof that “personalized medicine has arrived.” In fact, Goldman Sachs, a US-based investment bank, makes the case that it never will .

Cost/benefit analysis

Edward Abrahams, president of the Personalized Medicine Coalition (US-based), advocates for personalized medicine while noting in passing, market forces as represented by Goldman Sachs in his May 23, 2018 piece for statnews.com (Note: A link has been removed),

One of every four new drugs approved by the Food and Drug Administration over the last four years was designed to become a personalized (or “targeted”) therapy that zeros in on the subset of patients likely to respond positively to it. That’s a sea change from the way drugs were developed and marketed 10 years ago.

Some of these new treatments have extraordinarily high list prices. But focusing solely on the cost of these therapies rather than on the value they provide threatens the future of personalized medicine.

… most policymakers are not asking the right questions about the benefits of these treatments for patients and society. Influenced by cost concerns, they assume that prices for personalized tests and treatments cannot be justified even if they make the health system more efficient and effective by delivering superior, longer-lasting clinical outcomes and increasing the percentage of patients who benefit from prescribed treatments.

Goldman Sachs, for example, issued a report titled “The Genome Revolution.” It argues that while “genome medicine” offers “tremendous value for patients and society,” curing patients may not be “a sustainable business model.” [emphasis mine] The analysis underlines that the health system is not set up to reap the benefits of new scientific discoveries and technologies. Just as we are on the precipice of an era in which gene therapies, gene-editing, and immunotherapies promise to address the root causes of disease, Goldman Sachs says that these therapies have a “very different outlook with regard to recurring revenue versus chronic therapies.”

Let’s just chew on this one (contemplate)  for a minute”curing patients may not be ‘sustainable business model’!”

Coming down to earth: policy

While I find Gierczak to be over-enthused, he, like Abrahams, emphasizes the importance of new policy, in his case, the focus is Canadian policy. From Gierczak’s September 17, 2018 posting (Note: Links have been removed),

In Canada, companies need approval from Health Canada. But a 2004 law called the Assisted Human Reproduction Act (AHR Act) states that it’s a criminal offence “to alter the genome of a human cell, or in vitroembryo, that is capable of being transmitted to descendants”. The Actis so broadly written that Canadian scientists are prohibited from using the CRISPR-Cas9 technology on even somatic cells. Today, Canada is one of the few countries in the world where treating a disease with CRISPR-Cas9 is a crime.

On the other hand, some countries provide little regulatory oversight for editing either germ or somatic cells. In China, a company often only needs to satisfy the requirements of the local hospital where the treatment is being performed. And, if germ-cell editing goes wrong, there is little recourse for the future generations affected.

The AHR Act was introduced to regulate the use of reproductive technologies like in vitrofertilization and research related to cloning human embryos during the 1980s and 1990s. Today, we live in a time when medical science, and its role in Canadian society, is rapidly changing. CRISPR-Cas9 is a powerful tool, and there are aspects of the technology that aren’t well understood and could potentially put patients at risk if we move ahead too quickly. But the potential benefits are significant. Updated legislation that acknowledges both the risks and current realities of genomic engineering [emphasis mine] would relieve the current obstacles and support a path toward the introduction of safe new therapies.

Criminal ban on human gene-editing of inheritable cells (in Canada)

I had no idea there was a criminal ban on the practice until reading this January 2017 editorial by Bartha Maria Knoppers, Rosario Isasi, Timothy Caulfield, Erika Kleiderman, Patrick Bedford, Judy Illes, Ubaka Ogbogu, Vardit Ravitsky, & Michael Rudnicki for (Nature) npj Regenerative Medicine (Note: Links have been removed),

Driven by the rapid evolution of gene editing technologies, international policy is examining which regulatory models can address the ensuing scientific, socio-ethical and legal challenges for regenerative and personalised medicine.1 Emerging gene editing technologies, including the CRISPR/Cas9 2015 scientific breakthrough,2 are powerful, relatively inexpensive, accurate, and broadly accessible research tools.3 Moreover, they are being utilised throughout the world in a wide range of research initiatives with a clear eye on potential clinical applications. Considering the implications of human gene editing for selection, modification and enhancement, it is time to re-examine policy in Canada relevant to these important advances in the history of medicine and science, and the legislative and regulatory frameworks that govern them. Given the potential human reproductive applications of these technologies, careful consideration of these possibilities, as well as ethical and regulatory scrutiny must be a priority.4

With the advent of human embryonic stem cell research in 1978, the birth of Dolly (the cloned sheep) in 1996 and the Raelian cloning hoax in 2003, the environment surrounding the enactment of Canada’s 2004 Assisted Human Reproduction Act (AHRA) was the result of a decade of polarised debate,5 fuelled by dystopian and utopian visions for future applications. Rightly or not, this led to the AHRA prohibition on a wide range of activities, including the creation of embryos (s. 5(1)(b)) or chimeras (s. 5(1)(i)) for research and in vitro and in vivo germ line alterations (s. 5(1)(f)). Sanctions range from a fine (up to $500,000) to imprisonment (up to 10 years) (s. 60 AHRA).

In Canada, the criminal ban on gene editing appears clear, the Act states that “No person shall knowingly […] alter the genome of a cell of a human being or in vitro embryo such that the alteration is capable of being transmitted to descendants;” [emphases mine] (s. 5(1)(f) AHRA). This approach is not shared worldwide as other countries such as the United Kingdom, take a more regulatory approach to gene editing research.1 Indeed, as noted by the Law Reform Commission of Canada in 1982, criminal law should be ‘an instrument of last resort’ used solely for “conduct which is culpable, seriously harmful, and generally conceived of as deserving of punishment”.6 A criminal ban is a suboptimal policy tool for science as it is inflexible, stifles public debate, and hinders responsiveness to the evolving nature of science and societal attitudes.7 In contrast, a moratorium such as the self-imposed research moratorium on human germ line editing called for by scientists in December 20158 can at least allow for a time limited pause. But like bans, they may offer the illusion of finality and safety while halting research required to move forward and validate innovation.

On October 1st, 2016, Health Canada issued a Notice of Intent to develop regulations under the AHRA but this effort is limited to safety and payment issues (i.e. gamete donation). Today, there is a need for Canada to revisit the laws and policies that address the ethical, legal and social implications of human gene editing. The goal of such a critical move in Canada’s scientific and legal history would be a discussion of the right of Canadians to benefit from the advancement of science and its applications as promulgated in article 27 of the Universal Declaration of Human Rights9 and article 15(b) of the International Covenant on Economic, Social and Cultural Rights,10 which Canada has signed and ratified. Such an approach would further ensure the freedom of scientific endeavour both as a principle of a liberal democracy and as a social good, while allowing Canada to be engaged with the international scientific community.

Even though it’s a bit old, I still recommend reading the open access editorial in full, if you have the time.

One last thing abut the paper, the acknowledgements,

Sponsored by Canada’s Stem Cell Network, the Centre of Genomics and Policy of McGill University convened a ‘think tank’ on the future of human gene editing in Canada with legal and ethics experts as well as representatives and observers from government in Ottawa (August 31, 2016). The experts were Patrick Bedford, Janetta Bijl, Timothy Caulfield, Judy Illes, Rosario Isasi, Jonathan Kimmelman, Erika Kleiderman, Bartha Maria Knoppers, Eric Meslin, Cate Murray, Ubaka Ogbogu, Vardit Ravitsky, Michael Rudnicki, Stephen Strauss, Philip Welford, and Susan Zimmerman. The observers were Geneviève Dubois-Flynn, Danika Goosney, Peter Monette, Kyle Norrie, and Anthony Ridgway.

Competing interests

The authors declare no competing interests.

Both McGill and the Stem Cell Network pop up again. A November 8, 2017 article about the need for new Canadian gene-editing policies by Tom Blackwell for the National Post features some familiar names (Did someone have a budget for public relations and promotion?),

It’s one of the most exciting, and controversial, areas of health science today: new technology that can alter the genetic content of cells, potentially preventing inherited disease — or creating genetically enhanced humans.

But Canada is among the few countries in the world where working with the CRISPR gene-editing system on cells whose DNA can be passed down to future generations is a criminal offence, with penalties of up to 10 years in jail.

This week, one major science group announced it wants that changed, calling on the federal government to lift the prohibition and allow researchers to alter the genome of inheritable “germ” cells and embryos.

The potential of the technology is huge and the theoretical risks like eugenics or cloning are overplayed, argued a panel of the Stem Cell Network.

The step would be a “game-changer,” said Bartha Knoppers, a health-policy expert at McGill University, in a presentation to the annual Till & McCulloch Meetings of stem-cell and regenerative-medicine researchers [These meetings were originally known as the Stem Cell Network’s Annual General Meeting {AGM}]. [emphases mine]

“I’m completely against any modification of the human genome,” said the unidentified meeting attendee. “If you open this door, you won’t ever be able to close it again.”

If the ban is kept in place, however, Canadian scientists will fall further behind colleagues in other countries, say the experts behind the statement say; they argue possible abuses can be prevented with good ethical oversight.

“It’s a human-reproduction law, it was never meant to ban and slow down and restrict research,” said Vardit Ravitsky, a University of Montreal bioethicist who was part of the panel. “It’s a sort of historical accident … and now our hands are tied.”

There are fears, as well, that CRISPR could be used to create improved humans who are genetically programmed to have certain facial or other features, or that the editing could have harmful side effects. Regardless, none of it is happening in Canada, good or bad.

In fact, the Stem Cell Network panel is arguably skirting around the most contentious applications of the technology. It says it is asking the government merely to legalize research for its own sake on embryos and germ cells — those in eggs and sperm — not genetic editing of embryos used to actually get women pregnant.

The highlighted portions in the last two paragraphs of the excerpt were written one year prior to the claims by a Chinese scientist that he had run a clinical trial resulting in gene-edited twins, Lulu and Nana. (See my my November 28, 2018 posting for a comprehensive overview of the original furor). I have yet to publish a followup posting featuring the news that the CRISPR twins may have been ‘improved’ more extensively than originally realized. The initial reports about the twins focused on an illness-related reason (making them HIV ‘immune’) but made no mention of enhanced cognitive skills a side effect of eliminating the gene that would make them HIV ‘immune’. To date, the researcher has not made the bulk of his data available for an in-depth analysis to support his claim that he successfully gene-edited the twins. As well, there were apparently seven other pregnancies coming to term as part of the researcher’s clinical trial and there has been no news about those births.

Risk analysis innovation

Before moving onto the innovation of risk analysis, I want to focus a little more on at least one of the risks that gene-editing might present. Gierczak noted that CRISPR/Cas9 is “not perfect,” which acknowledges the truth but doesn’t convey all that much information.

While the terms ‘precision’ and ‘scissors’ are used frequently when describing the CRISPR technique, scientists actually mean that the technique is significantly ‘more precise’ than other techniques but they are not referencing an engineering level of precision. As for the ‘scissors’, it’s an analogy scientists like to use but in fact CRISPR is not as efficient and precise as a pair of scissors.

Michael Le Page in a July 16, 2018 article for New Scientist lays out some of the issues (Note: A link has been removed),

A study of CRIPSR suggests we shouldn’t rush into trying out CRISPR genome editing inside people’s bodies just yet. The technique can cause big deletions or rearrangements of DNA [emphasis mine], says Allan Bradley of the Wellcome Sanger Institute in the UK, meaning some therapies based on CRISPR may not be quite as safe as we thought.

The CRISPR genome editing technique is revolutionising biology, enabling us to create new varieties of plants and animals and develop treatments for a wide range of diseases.

The CRISPR Cas9 protein works by cutting the DNA of a cell in a specific place. When the cell repairs the damage, a few DNA letters get changed at this spot – an effect that can be exploited to disable genes.

At least, that’s how it is supposed to work. But in studies of mice and human cells, Bradley’s team has found that in around a fifth of cells, CRISPR causes deletions or rearrangements more than 100 DNA letters long. These surprising changes are sometimes thousands of letters long.

“I do believe the findings are robust,” says Gaetan Burgio of the Australian National University, an expert on CRISPR who has debunked previous studies questioning the method’s safety. “This is a well-performed study and fairly significant.”

I covered the Bradley paper and the concerns in a July 17, 2018 posting ‘The CRISPR ((clustered regularly interspaced short palindromic repeats)-CAS9 gene-editing technique may cause new genetic damage kerfuffle‘. (The ‘kerfufle’ was in reference to a report that the CRISPR market was affected by the publication of Bradley’s paper.)

Despite Health Canada not moving swiftly enough for some researchers, they have nonetheless managed to release an ‘outcome’ report about a consultation/analysis started in October 2016. Before getting to the consultation’s outcome, it’s interesting to look at how the consultation’s call for response was described (from Health Canada’s Toward a strengthened Assisted Human Reproduction Act ; A Consultation with Canadians on Key Policy Proposals webpage),

In October 2016, recognizing the need to strengthen the regulatory framework governing assisted human reproduction in Canada, Health Canada announced its intention to bring into force the dormant sections of the Assisted Human Reproduction Act  and to develop the necessary supporting regulations.

This consultation document provides an overview of the key policy proposals that will help inform the development of regulations to support bringing into force Section 10, Section 12 and Sections 45-58 of the Act. Specifically, the policy proposals describe the Department’s position on the following:

Section 10: Safety of Donor Sperm and Ova

  • Scope and application
  • Regulated parties and their regulatory obligations
  • Processing requirements, including donor suitability assessment
  • Record-keeping and traceability

Section 12: Reimbursement

  • Expenditures that may be reimbursed
  • Process for reimbursement
  • Creation and maintenance of records

Sections 45-58: Administration and Enforcement

  • Scope of the administration and enforcement framework
  • Role of inspectors designated under the Act

The purpose of the document is to provide Canadians with an opportunity to review the policy proposals and to provide feedback [emphasis mine] prior to the Department finalizing policy decisions and developing the regulations. In addition to requesting stakeholders’ general feedback on the policy proposals, the Department is also seeking input on specific questions, which are included throughout the document.

It took me a while to find the relevant section (in particular, take note of ‘Federal Regulatory Oversight’),

3.2. AHR in Canada Today

Today, an increasing number of Canadians are turning to AHR technologies to grow or build their families. A 2012 Canadian studyFootnote 1 found that infertility is on the rise in Canada, with roughly 16% of heterosexual couples experiencing infertility. In addition to rising infertility, the trend of delaying marriage and parenthood, scientific advances in cryopreserving ova, and the increasing use of AHR by LGBTQ2 couples and single parents to build a family are all contributing to an increase in the use of AHR technologies.

The growing use of reproductive technologies by Canadians to help build their families underscores the need to strengthen the AHR Act. While the approach to regulating AHR varies from country to country, Health Canada has considered international best practices and the need for regulatory alignment when developing the proposed policies set out in this document. …

3.2.1 Federal Regulatory Oversight

Although the scope of the AHR Act was significantly reduced in 2012 and some of the remaining sections have not yet been brought into force, there are many important sections of the Act that are currently administered and enforced by Health Canada, as summarized generally below:

Section 5: Prohibited Scientific and Research Procedures
Section 5 prohibits certain types of scientific research and clinical procedures that are deemed unacceptable, including: human cloning, the creation of an embryo for non-reproductive purposes, maintaining an embryo outside the human body beyond the fourteenth day, sex selection for non-medical reasons, altering the genome in a way that could be transmitted to descendants, and creating a chimera or a hybrid. [emphasis mine]

….

It almost seems as if the they were hiding the section that broached the human gene-editing question. It doesn’t seem to have worked as it appears, there are some very motivated parties determined to reframe the discussion. Health Canada’s ‘outocme’ report, published March 2019, What we heard: A summary of scanning and consultations on what’s next for health product regulation reflects the success of those efforts,

1.0 Introduction and Context

Scientific and technological advances are accelerating the pace of innovation. These advances are increasingly leading to the development of health products that are better able to predict, define, treat, and even cure human diseases. Globally, many factors are driving regulators to think about how to enable health innovation. To this end, Health Canada has been expanding beyond existing partnerships and engaging both domestically and internationally. This expanding landscape of products and services comes with a range of new challenges and opportunities.

In keeping up to date with emerging technologies and working collaboratively through strategic partnerships, Health Canada seeks to position itself as a regulator at the forefront of health innovation. Following the targeted sectoral review of the Health and Biosciences Sector Regulatory Review consultation by the Treasury Board Secretariat, Health Canada held a number of targeted meetings with a broad range of stakeholders.

This report outlines the methodologies used to look ahead at the emerging health technology environment, [emphasis mine] the potential areas of focus that resulted, and the key findings from consultations.

… the Department identified the following key drivers that are expected to shape the future of health innovation:

  1. The use of “big data” to inform decision-making: Health systems are generating more data, and becoming reliant on this data. The increasing accuracy, types, and volume of data available in real time enable automation and machine learning that can forecast activity, behaviour, or trends to support decision-making.
  2. Greater demand for citizen agency: Canadians increasingly want and have access to more information, resources, options, and platforms to manage their own health (e.g., mobile apps, direct-to-consumer services, decentralization of care).
  3. Increased precision and personalization in health care delivery: Diagnostic tools and therapies are increasingly able to target individual patients with customized therapies (e.g., individual gene therapy).
  4. Increased product complexity: Increasingly complex products do not fit well within conventional product classifications and standards (e.g., 3D printing).
  5. Evolving methods for production and distribution: In some cases, manufacturers and supply chains are becoming more distributed, challenging the current framework governing production and distribution of health products.
  6. The ways in which evidence is collected and used are changing: The processes around new drug innovation, research and development, and designing clinical trials are evolving in ways that are more flexible and adaptive.

With these key drivers in mind, the Department selected the following six emerging technologies for further investigation to better understand how the health product space is evolving:

  1. Artificial intelligence, including activities such as machine learning, neural networks, natural language processing, and robotics.
  2. Advanced cell therapies, such as individualized cell therapies tailor-made to address specific patient needs.
  3. Big data, from sources such as sensors, genetic information, and social media that are increasingly used to inform patient and health care practitioner decisions.
  4. 3D printing of health products (e.g., implants, prosthetics, cells, tissues).
  5. New ways of delivering drugs that bring together different product lines and methods (e.g., nano-carriers, implantable devices).
  6. Gene editing, including individualized gene therapies that can assist in preventing and treating certain diseases.

Next, to test the drivers identified and further investigate emerging technologies, the Department consulted key organizations and thought leaders across the country with expertise in health innovation. To this end, Health Canada held seven workshops with over 140 representatives from industry associations, small-to-medium sized enterprises and start-ups, larger multinational companies, investors, researchers, and clinicians in Ottawa, Toronto, Montreal, and Vancouver. [emphases mine]

The ‘outocme’ report, ‘What we heard …’, is well worth reading in its entirety; it’s about 9 pp.

I have one comment, ‘stakeholders’ don’t seem to include anyone who isn’t “from industry associations, small-to-medium sized enterprises and start-ups, larger multinational companies, investors, researchers, and clinician” or from “Ottawa, Toronto, Montreal, and Vancouver.” Aren’t the rest of us stakeholders?

Innovating risk analysis

This line in the report caught my eye (from Health Canada’s Toward a strengthened Assisted Human Reproduction Act ; A Consultation with Canadians on Key Policy Proposals webpage),

There is increasing need to enable innovation in a flexible, risk-based way, with appropriate oversight to ensure safety, quality, and efficacy. [emphases mine]

It reminded me of the 2019 federal budget (from my March 22, 2019 posting). One comment before proceeding, regulation and risk are tightly linked and, so, by innovating regulation they are by exttension alos innovating risk analysis,

… Budget 2019 introduces the first three “Regulatory Roadmaps” to specifically address stakeholder issues and irritants in these sectors, informed by over 140 responses [emphasis mine] from businesses and Canadians across the country, as well as recommendations from the Economic Strategy Tables.

Introducing Regulatory Roadmaps

These Roadmaps lay out the Government’s plans to modernize regulatory frameworks, without compromising our strong health, safety, and environmental protections. They contain proposals for legislative and regulatory amendments as well as novel regulatory approaches to accommodate emerging technologies, including the use of regulatory sandboxes and pilot projects—better aligning our regulatory frameworks with industry realities.

Budget 2019 proposes the necessary funding and legislative revisions so that regulatory departments and agencies can move forward on the Roadmaps, including providing the Canadian Food Inspection Agency, Health Canada and Transport Canada with up to $219.1 million over five years, starting in 2019–20, (with $0.5 million in remaining amortization), and $3.1 million per year on an ongoing basis.

In the coming weeks, the Government will be releasing the full Regulatory Roadmaps for each of the reviews, as well as timelines for enacting specific initiatives, which can be grouped in the following three main areas:

What Is a Regulatory Sandbox? Regulatory sandboxes are controlled “safe spaces” in which innovative products, services, business models and delivery mechanisms can be tested without immediately being subject to all of the regulatory requirements.
– European Banking Authority, 2017

Establishing a regulatory sandbox for new and innovative medical products
The regulatory approval system has not kept up with new medical technologies and processes. Health Canada proposes to modernize regulations to put in place a regulatory sandbox for new and innovative products, such as tissues developed through 3D printing, artificial intelligence, and gene therapies targeted to specific individuals. [emphasis mine]

Modernizing the regulation of clinical trials
Industry and academics have expressed concerns that regulations related to clinical trials are overly prescriptive and inconsistent. Health Canada proposes to implement a risk-based approach [emphasis mine] to clinical trials to reduce costs to industry and academics by removing unnecessary requirements for low-risk drugs and trials. The regulations will also provide the agri-food industry with the ability to carry out clinical trials within Canada on products such as food for special dietary use and novel foods.

Does the government always get 140 responses from a consultation process? Moving on, I agree with finding new approaches to regulatory processes and oversight and, by extension, new approaches to risk analysis.

Earlier in this post, I asked if someone had a budget for public relations/promotion. I wasn’t joking. My March 22, 2019 posting also included these line items in the proposed 2019 budget,

Budget 2019 proposes to make additional investments in support of the following organizations:
Stem Cell Network: Stem cell research—pioneered by two Canadians in the 1960s [James Till and Ernest McCulloch]—holds great promise for new therapies and medical treatments for respiratory and heart diseases, spinal cord injury, cancer, and many other diseases and disorders. The Stem Cell Network is a national not-for-profit organization that helps translate stem cell research into clinical applications and commercial products. To support this important work and foster Canada’s leadership in stem cell research, Budget 2019 proposes to provide the Stem Cell Network with renewed funding of $18 million over three years, starting in 2019–20.

Genome Canada: The insights derived from genomics—the study of the entire genetic information of living things encoded in their DNA and related molecules and proteins—hold the potential for breakthroughs that can improve the lives of Canadians and drive innovation and economic growth. Genome Canada is a not-for-profit organization dedicated to advancing genomics science and technology in order to create economic and social benefits for Canadians. To support Genome Canada’s operations, Budget 2019 proposes to provide Genome Canada with $100.5 million over five years, starting in 2020–21. This investment will also enable Genome Canada to launch new large-scale research competitions and projects, in collaboration with external partners, ensuring that Canada’s research community continues to have access to the resources needed to make transformative scientific breakthroughs and translate these discoveries into real-world applications.

Years ago, I managed to find a webpage with all of the proposals various organizations were submitting to a government budget committee. It was eye-opening. You can tell which organizations were able to hire someone who knew the current government buzzwords and the things that a government bureaucrat would want to hear and the organizations that didn’t.

Of course, if the government of the day is adamantly against or uninterested, no amount of persusasion will work to get your organization more money in the budget.

Finally

Reluctantly, I am inclined to explore the topic of emerging technologies such as gene-editing not only in the field of agriculture (for gene-editing of plants, fish, and animals see my November 28, 2018 posting) but also with humans. At the very least, it needs to be discussed whether we choose to participate or not.

If you are interested in the arguments against changing Canada’s prohibition against gene-editing of humans, there’s an Ocotber 2, 2017 posting on Impact Ethics by Françoise Baylis, Professor and Canada Research Chair in Bioethics and Philosophy at Dalhousie University, and Alana Cattapan, Johnson Shoyama Graduate School of Public Policy at the University of Saskatchewan, which makes some compelling arguments. Of course, it was written before the CRISPR twins (my November 28, 2018 posting).

Recaliing CRISPR Therapeutics (mentioned by Gierczak), the company received permission to run clinical trials in the US in October 2018 after the FDA (US Food and Drug Administration) lifted an earlier ban on their trials according to an Oct. 10, 2018 article by Frank Vinhuan for exome,

The partners also noted that their therapy is making progress outside of the U.S. They announced that they have received regulatory clearance in “multiple countries” to begin tests of the experimental treatment in both sickle cell disease and beta thalassemia, …

It seems to me that the quotes around “multiple countries” are meant to suggest doubt of some kind. Generally speaking, company representatives make those kinds of generalizations when they’re trying to pump up their copy. E.g., 50% increase in attendance  but no whole numbers to tell you what that means. It could mean two people attended the first year and then brought a friend the next year or 100 people attended and the next year there were 150.

Despite attempts to declare personalized medicine as having arrived, I think everything is still in flux with no preordained outcome. The future has yet to be determined but it will be and I , for one, would like to have some say in the matter.

S.NET (Society for the Study of New and Emerging Technologies) 2019 conference in Quito, Ecuador: call for abstracts

Why isn’t the S.NET abbreviation SSNET? That’s what it should be, given the organization’s full name: Society for the Study of New and Emerging Technologies. S.NET smacks of a compromise or consensus decision of some kind. Also, the ‘New’ in its name was ‘Nanoscience’ at one time (see my Oct. 22, 2013 posting).

Now onto 2019 and the conference, which, for the first time ever, is being held in Latin America. Here’s more from a February 4, 2019 S.Net email about the call for abstracts,

2019 Annual S.NET Meeting
Contrasting Visions of Technological Change

The 11th Annual S.NET meeting will take place November 18-20, 2019, at the Latin American Faculty of Social Sciences in Quito, Ecuador.

This year’s meeting will provide rich opportunities to reflect on technological change by establishing a dialogue between contrasting visions on how technology becomes closely intertwined with social orders.  We aim to open the black box of technological change by exploring the sociotechnical agreements that help to explain why societies follow certain technological trajectories. Contributors are invited to explore the ramifications of technological change, reflect on the policy process of technology, and debate whether or why technological innovation is a matter for democracy.

Following the transnational nature of S.NET, the meeting will highlight the diverse geographical and cultural approaches to technological innovation, the forces driving sociotechnical change, and social innovation.  It is of paramount importance to question the role of technology in the shaping of society and the outcomes of these configurations.  What happens when these arrangements come into being, are transformed or fall apart?  Does technology create contestation?  Why and how should we engage with contested visions of technology change?

This is the first time that the S.NET Meeting will take place in Latin America and we encourage panels and presentations with contrasting voices from both the Global North and the Global South. 

Topics of interest include, but are not limited to:

Sociotechnical imaginaries of innovation
The role of technology on shaping nationhood and nation identities
Decision-making processes on science and technology public policies
Co-creation approaches to promote public innovation
Grassroots innovation, sustainability and democracy
Visions and cultural imaginaries
Role of social sciences and humanities in processes technological change
In addition, we welcome contributions on:
Research dynamics and organization Innovation and use
Governance and regulation
Politics and ethics
Roles of publics and stakeholders

Keynote Speakers
TBA (check the conference website for updates!)

Deadlines & Submission Instructions
The program committee invites contributions from scholars, technology developers and practitioners, and welcome presentations from a range of disciplines spanning the humanities, social and natural sciences.  We invite individual paper submissions, open panel and closed session proposals, student posters, and special format sessions, including events that are innovative in form and content. 

The deadline for abstract submissions is *April 18, 2019* [extended to May 12, 2019].  Abstracts should be approximately 250 words in length, emailed in PDF format to 2019snet@gmail.com.  Notifications of acceptance can be expected by May 30, 2019.

Junior scholars and those with limited resources are strongly encouraged to apply, as the organizing committee is actively investigating potential sources of financial support.

Details on the conference can be found here: https://www.flacso.edu.ec/snet2019/

Local Organizing Committee
María Belén Albornoz, Isarelis Pérez, Javier Jiménez, Mónica Bustamante, Jorge Núñez, Maka Suárez.

Venue
FLACSO Ecuador is located in the heart of Quito.  Most hotels, museums, shopping centers and other cultural hotspots in the city are located near the campus and are easily accessible by public or private transportation.  Due to its proximity and easy access, Meeting participants would be able to enjoy Quito’s rich cultural life during their stay.  

About S.NET
S.NET is an international association that promotes intellectual exchange and critical inquiry about the advancement of new and emerging technologies in society.  The aim of the association is to advance critical reflection from various perspectives on developments in a broad range of new and emerging fields, including, but not limited to, nanoscale science and engineering, biotechnology, synthetic biology, cognitive science, ICT and Big Data, and geo-engineering.  Current S.NET board members are: Michael Bennett (President), Maria Belen Albornoz, Claire Shelley-Egan, Ana Delgado, Ana Viseu, Nora Vaage, Chris Toumey, Poonam Pandey, Sylvester Johnson, Lotte Krabbenborg, and Maria Joao Ferreira Maia.

Don’t forget, the deadline for your abstract is *April 18, 2019* [extended to May 12, 2019].

For anyone curious about what Quito might look like, there’s this from Quito’s Wikipedia entry,

Clockwise from top: Calle La Ronda, Iglesia de la Compañía de Jesús, El Panecillo as seen from Northern Quito, Carondelet Palace, Central-Northern Quito, Parque La Carolina and Iglesia y Monasterio de San Francisco. Credit: various authors – montage of various important landmarks of the City of Quito, Ecuador taken from files found in Wikimedia Commons. CC BY-SA 3.0 File:Montaje Quito.png Created: 24 December 2012

Good luck to all everyone submitting an abstract.

*Date for abstract submissions changed from April 18, 2019 to May 12, 2019 on April 24, 2019