Tag Archives: China

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

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

But a discussion does need to happen

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This paper is behind a paywall.

A couple of final comments

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The interest flurry

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

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

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

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

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

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

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

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

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

Who did the experiments?

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

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

What did they actually do?

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

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

Wait, other human embryos have been edited before?

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

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

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

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

What did the American team do differently?

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

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

Is this kind of research even legal?

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

Why would you want to edit embryos at all?

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

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

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

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

Does this discovery have any social importance at all?

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

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

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

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

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

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

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

Impressive results

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

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

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

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

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

A brave new world?

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

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

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

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

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

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

Introduction to CRISPR

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

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

Oregon team

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

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

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

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

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

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

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

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

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

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

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

This paper appears to be open access.

CRISPR Issues: ethics and patents

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

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

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

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

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

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

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

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

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

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

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

….

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

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

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

This, too, is a good and thoughtful read.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

….

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

-30-

Part 2 covers three critical responses to the reporting and between them describe the technology in more detail and the possibility of ‘designer babies’.  CRISPR and editing the germline in the US (part 2 of 3): ‘designer babies’?

Part 3 is all about public discussion or, rather, the lack of and need for according to a couple of social scientists. Informally, there is some discussion via pop culture and Joelle Renstrom notes although she is focused on the larger issues touched on by the television series, Orphan Black and as I touch on in my final comments. CRISPR and editing the germline in the US (part 3 of 3): public discussions and pop culture

The greatest intellectual theft in history? Tea!

Following my green tea and sensitive teeth story (August 4, 2017 posting), I stumbled on this August 2, 2017 story by Nicola Twilley and Cynthia Graber for The Atlantic,

… The Chinese domesticated tea over thousands of years, but they lost their near monopoly on international trade when a Scottish botanist, disguised as a Chinese nobleman, smuggled it out of China in the 1800s, in order to secure Britain’s favorite beverage and prop up its empire for another century. The story involves pirates, ponytails, and hard drugs—and, to help tell the tale, Cynthia and Nicky visit Britain’s one and only commercial tea plantation, tucked away in a secret garden on an aristocratic estate on the Cornish coast. While harvesting and processing tea leaves, we learn the difference between green and black tea, as well as which is better for your health. Put the kettle on, and settle in for the science and history of tea!

A podcast from Gastropod (Nicola Twilley’s and Cynthia Graber’s blog) is embedded into The Atlantic story but you can also find it here on the Gastropod website along with more details in the accompanying text (Note: Links have been removed),

It seemed so simple in the mid-1700s: China had tea, Britain wanted tea. First introduced by Portuguese princess Catherine de Braganza in 1662, tea soon overtook beer as Britain’s favorite brew. The only problem, according to Sarah Rose, author of For All the Tea in China: How England Stole the World’s Favorite Drink and Changed History, was that the Chinese weren’t purchasing any British goods in return. Britain was simply dumping its silver into China, creating a serious balance of payments problem. Britain’s solution? Trade drugs for drugs—specifically, the caffeine fix in tea for the poppies that grow abundantly on the Afghan-Pakistan border, which at the time was part of the British empire. “They just start dumping opium into China,” explained Rose. But drug-dealing proved to be an expensive headache, and so, in 1848, Britain embarked on the biggest botanical heist in history, as well as one of the biggest thefts of intellectual property to date: stealing Chinese tea plants, as well as Chinese tea-processing expertise, in order to create a tea industry in India.

I first wrote about Robert Fortune, master thief and scientist and Sarah Rose, author of ‘For All the Tea in China: How England Stole the World’s Favorite Drink and Changed History‘ (2011) in the context of computer chips, US and China relations, and piracy fears (my Aug. 11, 2010 posting).

In the Gastropod podcast, Rose seems to be willing to give more details from her book now that it’s no longer fresh off the press. Amongst other gems, you’ll find out that Fortune was six feet* or more in height, had shaved himself bald and had a queue sewn into his scalp, couldn’t speak any Chinese languages, and was a white Scotsman. How did he pass? It had to do with how the Chinese in that period viewed ‘foreigness’; for more details you’ll need to listed to the podcast. Rose also mentions the British East India Company, a quasi-government (they had their own army) , in some jurisdictions, and pirates.

As regular readers know, I have often featured intellectual property stories here and while this doesn’t seem to fit into my emerging technologies focus, arguably, tea could be described as an emerging technology (albeit stolen from China) for the British Empire at that time.

I strongly suggest listening to and/or reading the July 31, 2017 Gastropod posting in its entirety.

*One quick comment, I had a professor some years ago who was involved with various Chinese ethnic groups who were to be displaced by the massive ‘Three Gorges Project’ and learned this. The Han people are dominant in China but my professor noted there are others including are least one ethnic group where males are six feet and taller and the females five foot 10 inches and taller due to their preference for eating buckwheat rather than white rice as their main grain. Robert Fortune’s height may not have been quite as unusual as I would have believed prior to that lecture.

Nano with green tea for sensitive teeth

The future will be beautiful if scientists are successful with a new DNA (deoxyribonucleic acid) sunscreen (my Aug. 3, 2017 posting) and a new dental material for people with sensitive teeth. From an Aug. 2, 2017 news item on phys.org,

An ice cold drink is refreshing in the summer, but for people with sensitive teeth, it can cause a painful jolt in the mouth. This condition can be treated, but many current approaches don’t last long. Now researchers report in the journal ACS [American Chemical Society] Applied Materials & Interfaces the development of a new material with an extract from green tea that could fix this problem—and help prevent cavities in these susceptible patients.

An Aug. 2, 2017 ACS news release, which originated the news item, describes the problem and the work in more detail,

Tooth sensitivity commonly occurs when the protective layers of teeth are worn away, revealing a bony tissue called dentin. This tissue contains microscopic hollow tubes that, when exposed, allow hot and cold liquids and food to contact the underlying nerve endings in the teeth, causing pain. Unprotected dentin is also vulnerable to cavity formation. Plugging these tubes with a mineral called nanohydroxyapatite is a long-standing approach to treating sensitivity. But the material doesn’t stand up well to regular brushing, grinding, erosion or acid produced by cavity-causing bacteria. Cui Huang and colleagues wanted to tackle sensitivity and beat the bacteria at the same time.

The researchers encapsulated nanohydroxyapatite and a green tea polyphenol — epigallocatechin-3-gallate, or EGCG — in silica nanoparticles, which can stand up to acid and wear and tear. EGCG has been shown in previous studies to fight Streptococcus mutans, which forms biofilms that cause cavities. Testing on extracted wisdom teeth showed that the material plugged the dentin tubules, released EGCG for at least 96 hours, stood up to tooth erosion and brushing and prevented biofilm formation. It also showed low toxicity. Based on these findings, the researchers say the material could indeed be a good candidate for combating tooth sensitivity and cavities.

The authors acknowledge funding from the National Natural Science Foundation of China, the Natural Science Foundation of Hubei Province of China and the Fundamental Research Funds for the Central Universities.

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

Development of Epigallocatechin-3-gallate-Encapsulated Nanohydroxyapatite/Mesoporous Silica for Therapeutic Management of Dentin Surface by Jian Yu, Hongye Yang, Kang Li, Hongyu Ren, Jinmei Lei, and Cui Huang. ACS Appl. Mater. Interfaces, Article ASAP DOI: 10.1021/acsami.7b06597 Publication Date (Web): July 13, 2017

Copyright © 2017 American Chemical Society

This paper is behind a paywall.

Followup on Pashmina nanotech tag story

I’m not sure if this is the same initiative as the one I described in my Feb. 27, 2013 posting about nanotechnology-enabled anti-counterfeiting labels for Pashmina shawls and other products but it seems likely. From a May 16, 2017 article by Athar Parvaiz for factordaily.com,

Until a few years ago, if you were buying a coveted Kashmiri Pashmina, chances were you’d be worried about being sold a fake. Despite having a geographical indications (GI) tag, fakes and machine-made shawls abound in the market.

But a couple of years ago, the Jammu and Kashmir (J&K) government decided to take things in its hands and reinstate buyers’ faith in the Rs 2,000-crore industry, which provides employment to around 300,000 people. It started using nanotechnology to label Pashmina products like shawls, mufflers and stoles to ensure authenticity.

Pashmina artisans say the move has benefitted them greatly, and most of them prefer to sell certified products as they get full price for the authenticated shawls. Experts from the Pashmina Testing and Quality Certification Centre (PTQCC) said they label about 500 shawls per month, which is almost all the products produced in the state, as the number hardly crosses 500 to 600 per month these days.

Gowhar Ahmad, a Pashmina artist from downtown Srinagar, says he’s sold several shawls with authentication labels since the laboratory was established in 2015. “However, customers repeatedly ask about the authenticity of my products as most of them haven’t heard of the certification. When I tell them about it, they run searches on their phones and only then are they convinced,” he said.

“The government should spread information about how it is ensuring the authenticity of Pashmina shawls,” Ahmad said. He added the labelled shawls fetch full price while machine-made products don’t even get half.

Another artist, Nazir Ahmad from Eidgah in Srinagar, agreed that the labelling is helpful, and reiterated Gowhar’s point about the need to spread the word about it outside Kashmir. “The government should also set up more laboratories for certification of Pashmina products,” he added. At present an artisan has to wait for up to seven days to get a shawl labelled. With more laboratories, the wait time can be reduced, he said.

These artisans may soon have reason to cheer. Mustaq Ahmad Shah, assistant director of handicrafts in Srinagar, said the handicrafts department plans to launch an extensive advertising campaign “to spread information on how to tell apart genuine and fake pashmina products following the recent steps taken by the state government to maintain the purity and glory of this heritage industry.” The department is also considering creating more PTQCC  facilities for the benefit of Pashmina artisans, he added.

Parvaiz describes the difference between authentic Pashmina wool products and the counterfeit products, as well as, the certification process,

According to experts, fake Pashmina-makers add nylon to below-standard Pashmina from Mongolia and China so that it can withstand the pressure of being spun on automatic machines. These shawls appear deceptively similar to genuine handmade Pashmina and most buyers get easily duped.

“But, after three-four years, the wool fibre starts shrinking and separating from the nylon, especially after washing,” Yasir Ahmad Mir, a professor at Srinagar’s Craft Development Institute (CDI) said. The extremely fine fibre of Pashmina can’t be spun by machine; it can be only hand-spun, he added.

“We do laboratory tests to determine whether the Pashmina is hand-spun or machine-spun and whether the shawl has been hand-woven or machine-made,” said Younus Farooq, manager at the PTQCC.

If a product withstands the scrutiny of laboratory testing, it gets a a non-detachable secure fusion authentication label (microchip) containing nano-particles with a unique layering code, readable under infrared light. The label contains information about the product along with a unique number. It is stuck on the Pashmina product with the help of heat without compromising on its aesthetics.

It was nice to find a followup article all these years later.

La Machine, Ottawa (Canada), and the Canada Aviation and Space Museum

First, you have to see the video,

La Machine

The ‘dragon’ and the ‘spider’ have sprung forth from a French street theatre group known as La Machine and the  La Machine ‘experience’ is making its début in North America in Ottawa, Ontario (July 27 – 30, 2017) as part of Canada’s 150th celebration.

Here’s more about La Machine and the ‘experience’ from the city of Ottawa’s event page,

Making its debut in North America, La Machine will captivate the public with its travelling urban theatre in the streets of downtown Ottawa.

Wandering around in public spaces, the protagonists will invade the heart of the capital in a show entitled “The Spirit of the Dragon-Horse, With Stolen Wings”. They will live among us for 24 hours a day over the course of four days as they pursue their quest and fulfill their destiny.

LongMa

Part dragon and part horse, LongMa stands 12 metres high, 5 metres wide and weighs 45 tons. Although his body is made of wood and steel, we quickly fall under his spell and connect with him on an ethereal level. From the top of his hooves, he trots with elegance, gallops, rears himself up and lies down.

With his piercing gaze, LongMa scours the crowd and interacts with them thanks as his neck rises, lowers and oscillates from left to right. His ribcage swells under the pressure of his lungs. But be careful, the warm breath coming out of his nostrils could quickly be transformed into fire coming out of his mouth.

The Spider

Beautiful and repulsive, aggressive and gentle, the giant spider will give you chills. Her eight legs and body that synchronize as she crawls around town gracefully. Like a dancer, she wanders, steps over trees, streetlights and bus shelters… At rest, she is 5.7 metres high and 6 metres wide, but she can reach up to 13 metres when in motion.  Fully outstretched, she is about 20 metres long.

Will she extinguish LongMa’s flames with the water deployed from her abdomen?

Credit: Jordi Bover


About La Machine Company

La Machine is a street theatre company founded in 1999 and leaded by François Delarozière. Its conception is thanks to artists, technicians and theatre designers working together for the construction of unusual theatre objects. Today, La Machine develops many projects in the field of urban development as well as for street theatre. At the heart of La Machine’s artistic approach, movement is read as a language, as a source of emotion. Through each of these living architectures, the idea is to dream of tomorrow’s cities, and thanks to this, transform the way we look at our towns. To bring its creations to life, La Machine has set up two workshops, one in Nantes and one in Tournefeuille. They bring together many different trades and crafts from theatre and the arts, to industry and advanced technology. People and their skills are the very essence of the creative process.

Ottawa and La Machine

I think this Ottawa event is much more engaging than Toronto’s giant rubber duck (which has proved to be controversial( e.g. June ?, 2017 posting on blogTO and Alina Bykova’s June 30, 3017 article for thestar.com) on July 1, 2017. Getting back to Ottawa, Judy Trinh’s June 1, 2016 article for CBC (Canadian Broadcasting Corporation) news online previews and provides some inside scoop about the 2017 event (Note: A link has been removed),

A giant mechanical dragon and spider from France will roam the streets of Ottawa next summer as part of celebrations for Canada’s 150th birthday.

It will be the first time the fire-breathing and water spraying creatures invade North America.

Securing the performance of the monsters from La Machine, a production company based in Nantes, France comes at a cost of $3 million — an amount that will be shared by both the public and private sector.

The Ottawa 2017 organizing committee has been working on booking the show for nearly a year and a half.

Negotiations didn’t just involve the City of Ottawa and the French production company. It also involved a Chinese businessman — Adam Yu, an entrepreneur based in Beijing who owns the rights to the dragon for La Machine.

Laflamme [executive director of Ottawa 2017, Guy Laflamme] said mayor Jim Watson set aside time during his economic mission to China to meet with Yu and make the case for loaning the dragon to Ottawa.

Organizers have just started “storyboarding” the show with La Machine’s artistic director, François Delarozière.

Although he’s reticent to describe what the show will look like, Laflamme does provide some hints: the operators will be dressed like they stepped out of the movie, The Matrix [movi e description], and the giant robots will make stops at Ottawa landmarks and interact with spectators.

Local musicians will also be hired to form a travelling orchestra for the soundtrack to the dragon’s and spider’s adventures.

If I read that rightly, planning seems to have started in 2014.

Canada Aviation and Space Museum

While La Machine is in Ottawa with their mechanicals, there will be a preview (from an Ingenium [formerly Canada Science and Technology Museums Corporation] July 12, 2017 notice received via email), Note: Links have been removed,

EXCLUSIVE SNEAK PEEK
Presented as part of Ottawa 2017

Making its debut in North America, _La Machine_ will captivate the
public with its dramatic urban theatre experience – and you can get
exclusive access at the Canada Aviation and Space Museum!

From July 15 to 24 [2017; emphasis mine], the Museum will be hosting a variety of
larger-than-life activities leading up to the big performance.
Activities include special viewing areas, a mini exhibition about _La
Machine_, a film about Long Ma the Dragon-Horse, creative activities and
a special lecture with _La Machine_’s creator. All activities are FREE
with Museum admission. Find out more by visiting our website.   [3]

SPECIAL LECTURE
THE MAKING OF_ LA MACHINE_ WITH FRANÇOIS DELAROZIÈRE
Join François Delarozière, the visionary artistic director and
engineer behind the wonders of _La Machine_, for an afternoon of insight
and conversation exploring the street theatre company’s history and
the creative process behind its fantastical mechanical masterpieces.
(Bilingual presentation)

Saturday, July 15, 2017
2 p.m. to 3 p.m.
Canada Aviation and Space Museum
Mauril Bélanger Theatre

SPACE IS LIMITED, REGISTER HERE!  [4]

[5]

UN AVANT-GOÛT EXCLUSIF

Présenté dans le cadre d’Ottawa 2017

Pour la première fois en Amérique du Nord,_ La Machine_ s’apprête
à captiver le public avec son impressionnant théâtre urbain. De plus,
vous aurez droit à un accès exclusif au Musée de l’aviation et de
l’espace du Canada!

Du 15 au 24 juillet, le Musée tiendra une série d’activités hors du
commun dans l’attente de la grande représentation.  On y comptera des
projections spéciales; une mini-exposition sur _La Machine_; un film
racontant l’histoire de Long Ma, le cheval-dragon; des activités
créatives et une conférence spéciale en compagnie du créateur de _La
Machine_. Tous les activités sont comprises dans le prix d’entrée au
Musée.  Visitez notre site Web [6] pour obtenir plus de renseignements.

CONFÉRENCE SPÉCIALE
LA RÉALISATION DE _LA MACHINE_ AVEC FRANÇOIS DELAROZIÈRE
Venez échanger avec François Delarozière, directeur artistique de _La
Machine_ et concepteur visionnaire de ces merveilles mécaniques, et
découvrez l’histoire de cette compagnie de théâtre de rue et le
processus ayant mené à la création de ses fantastiques
chefs-d’œuvre mécaniques.  (Présentation bilingue)

Samedi 15 juillet 2017
De 14 h à 15 h
Musée de l’aviation et de l’espace du Canada
Théâtre Mauril Bélanger

INSCRIVEZ-VOUS ICI – LE NOMBRE DE PLACES EST LIMITÉ!  [7]

You can sign up for the talk with François Delarozière here. It is a bilingual presentation included with the entrance fee (as noted previously) to the museum entitling you to a seat assuming you sign up quickly.

For the curious, you can find more about La Machine at its website. The images on the banner are stunning.

In scientific race US sees China coming up from rear

Sometime it seems as if scientific research is like a race with everyone competing for first place. As in most sports, there are multiple competitions for various sub-groups but only one important race. The US has held the lead position for decades although always with some anxiety. These days the anxiety is focused on China. A June 15, 2017 news item on ScienceDaily suggests that US dominance is threatened in at least one area of research—the biomedical sector,

American scientific teams still publish significantly more biomedical research discoveries than teams from any other country, a new study shows, and the U.S. still leads the world in research and development expenditures.

But American dominance is slowly shrinking, the analysis finds, as China’s skyrocketing investing on science over the last two decades begins to pay off. Chinese biomedical research teams now rank fourth in the world for total number of new discoveries published in six top-tier journals, and the country spent three-quarters what the U.S. spent on research and development during 2015.

Meanwhile, the analysis shows, scientists from the U.S. and other countries increasingly make discoveries and advancements as part of teams that involve researchers from around the world.

A June 15, 2017 Michigan Medicine University of Michigan news release (also on EurekAlert), which originated the news item, details the research team’s insights,

The last 15 years have ushered in an era of “team science” as research funding in the U.S., Great Britain and other European countries, as well as Canada and Australia, stagnated. The number of authors has also grown over time. For example, in 2000 only two percent of the research papers the new study looked include 21 or more authors — a number that increased to 12.5 percent in 2015.

The new findings, published in JCI Insight by a team of University of Michigan researchers, come at a critical time for the debate over the future of U.S. federal research funding. The study is based on a careful analysis of original research papers published in six top-tier and four mid-tier journals from 2000 to 2015, in addition to data on R&D investment from those same years.

The study builds on other work that has also warned of America’s slipping status in the world of science and medical research, and the resulting impact on the next generation of aspiring scientists.

“It’s time for U.S. policy-makers to reflect and decide whether the year-to-year uncertainty in National Institutes of Health budget and the proposed cuts are in our societal and national best interest,” says Bishr Omary, M.D., Ph.D., senior author of the new data-supported opinion piece and chief scientific officer of Michigan Medicine, U-M’s academic medical center. “If we continue on the path we’re on, it will be harder to maintain our lead and, even more importantly, we could be disenchanting the next generation of bright and passionate biomedical scientists who see a limited future in pursuing a scientist or physician-investigator career.”

The analysis charts South Korea’s entry into the top 10 countries for publications, as well as China’s leap from outside the top 10 in 2000 to fourth place in 2015. They also track the major increases in support for research in South Korea and Singapore since the start of the 21st Century.

Meticulous tracking

First author of the study, U-M informationist Marisa Conte, and Omary co-led a team that looked carefully at the currency of modern science: peer-reviewed basic science and clinical research papers describing new findings, published in journals with long histories of accepting among the world’s most significant discoveries.

They reviewed every issue of six top-tier international journals (JAMA, Lancet, the New England Journal of Medicine, Cell, Nature and Science), and four mid-ranking journals (British Medical Journal, JAMA Internal Medicine, Journal of Cell Science, FASEB Journal), chosen to represent the clinical and basic science aspects of research.

The analysis included only papers that reported new results from basic research experiments, translational studies, clinical trials, metanalyses, and studies of disease outcomes. Author affiliations for corresponding authors and all other authors were recorded by country.

The rise in global cooperation is striking. In 2000, 25 percent of papers in the six top-tier journals were by teams that included researchers from at least two countries. In 2015, that figure was closer to 50 percent. The increasing need for multidisciplinary approaches to make major advances, coupled with the advances of Internet-based collaboration tools, likely have something to do with this, Omary says.

The authors, who also include Santiago Schnell, Ph.D. and Jing Liu, Ph.D., note that part of their group’s interest in doing the study sprang from their hypothesis that a flat NIH budget is likely to have negative consequences but they wanted to gather data to test their hypothesis.

They also observed what appears to be an increasing number of Chinese-born scientists who had trained in the U.S. going back to China after their training, where once most of them would have sought to stay in the U.S. In addition, Singapore has been able to recruit several top notch U.S. and other international scientists due to their marked increase in R&D investments.

The same trends appear to be happening in Great Britain, Australia, Canada, France, Germany and other countries the authors studied – where research investing has stayed consistent when measured as a percentage of the U.S. total over the last 15 years.

The authors note that their study is based on data up to 2015, and that in the current 2017 federal fiscal year, funding for NIH has increased thanks to bipartisan Congressional appropriations. The NIH contributes to most of the federal support for medical and basic biomedical research in the U.S. But discussion of cuts to research funding that hinders many federal agencies is in the air during the current debates for the 2018 budget. Meanwhile, the Chinese R&D spending is projected to surpass the U.S. total by 2022.

“Our analysis, albeit limited to a small number of representative journals, supports the importance of financial investment in research,” Omary says. “I would still strongly encourage any child interested in science to pursue their dream and passion, but I hope that our current and future investment in NIH and other federal research support agencies will rise above any branch of government to help our next generation reach their potential and dreams.”

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

Globalization and changing trends of biomedical research output by Marisa L. Conte, Jing Liu, Santiago Schnell, and M. Bishr Omary. JCI Insight. 2017;2(12):e95206 doi:10.1172/jci.insight.95206 Volume 2, Issue 12 (June 15, 2017)

Copyright © 2017, American Society for Clinical Investigation

This paper is open access.

The notion of a race and looking back to see who, if anyone, is gaining on you reminded me of a local piece of sports lore, the Roger Banister-John Landy ‘Miracle Mile’. In the run up to the 1954 Commonwealth Games held in Vancouver, Canada, two runners were known to have broken the 4-minute mile limit (previously thought to have been impossible) and this meeting was considered an historic meeting. Here’s more from the miraclemile1954.com website,

On August 7, 1954 during the British Empire and Commonwealth Games in Vancouver, B.C., England’s Roger Bannister and Australian John Landy met for the first time in the one mile run at the newly constructed Empire Stadium.

Both men had broken the four minute barrier previously that year. Bannister was the first to break the mark with a time of 3:59.4 on May 6th in Oxford, England. Subsequently, on June 21st in Turku, Finland, John Landy became the new record holder with an official time of 3:58.

The world watched eagerly as both men approached the starting blocks. As 35,000 enthusiastic fans looked on, no one knew what would take place on that historic day.

Promoted as “The Mile of the Century”, it would later be known as the “Miracle Mile”.

With only 90 yards to go in one of the world’s most memorable races, John Landy glanced over his left shoulder to check his opponent’s position. At that instant Bannister streaked by him to victory in a Commonwealth record time of 3:58.8. Landy’s second place finish in 3:59.6 marked the first time the four minute mile had been broken by two men in the same race.

The website hosts an image of the moment memorialized in bronze when Landy looks to his left as Banister passes him on his right,

By Statue: Jack HarmanPhoto: Paul Joseph from vancouver, bc, canada – roger bannister running the four minute mileUploaded by Skeezix1000, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=9801121

Getting back to science, I wonder if some day we’ll stop thinking of it as a race where, inevitably, there’s one winner and everyone else loses and find a new metaphor.

Nanotechnology-enabled warming textile being introduced at Berlin (Germany) Fashion Week July 4 – 7, 2017

Acanthurus GmbH, a Frankfurt-based (Germany) nanotechnology company announced its participation in Berlin Fashion Week’s (July 4 – 7, 2017) showcase for technology in fashion, Panorama Berlin  (according to Berlin Fashion Week’s Fashion Fair Highlights in July 2017 webpage; scroll down to Panorama Berlin subsection).

Here are more details about Acanthurus’ participation from a July 4, 2017 news item on innovationintextiles.com,

This week, Frankfurt-based nanotechnology company Acanthurus GmbH will introduce its innovative nanothermal warming textile technology nanogy at the Berlin FashionTech exhibition. An innovative warming technology was developed by Chinese market leader j-NOVA for the European market, under the brand name nanogy.

A July 3, 2017 nanogy press release, which originated the news item, offers another perspective on the story,

Too cold for your favorite dress? Leave your heavy coat at home and stay warm with ground-breaking nanotechnology instead.

Frankfurt-based nano technology company Acanthurus GmbH has brought an innovative warming technology developed by Chinese market leader j-NOVA© to the European market, under the brand name nanogy. “This will make freezing a thing of the past,” says Carsten Wortmann, founder and CEO of Acanthurus GmbH. The ultra-light, high-tech textiles can be integrated into any garment – including that go-to jacket everyone loves to wear on chilly days. All you need is a standard power bank to feel the warmth flow through your body, even on the coldest of days.

The innovative, lightweight technology is completely non-metallic, meaning it emits no radiation. The non-metallic nature of the technology allows it to be washed at any temperature, so there’s no need to worry about accidental spillages, whatever the circumstances. The technology is extremely thin and flexible and, as there is absolutely no metal included, can be scrunched or crumpled without damaging its function. This also means that the technology can be integrated into garments without any visible lines or hems, making it the optimal solution for fashion and textile companies alike.

nanogy measures an energy conversion rate of over 90%, making it one of the most sustainable and environmentally friendly warming solutions ever developed. The technology is also recyclable, so consumers can dispose of it as they would any other garment.

“Our focus is not just to provide world class technology, but also to improve people’s lives without harming our environment. We call this a nanothermal experience, and our current use cases have only covered a fraction of potential opportunities,” says Jeni Odley, Director of Acanthurus GmbH. As expected for any modern tech company, users can even control the temperature of the textile with a mobile app, making the integration of nanogy a simplified, one-touch experience.

I wasn’t able to find much about j-Nova but there was this from the ISPO Munich 2017 exhibitor details webpage,

j-NOVA.WORKS Co., Ltd.

4-B302, No. 328 Creative Industry Park, Xinhu St., Suzhou Industrial Park
215123 Jiangsu Prov.
China
P  +49 69 130277-70
F  +49 69 130277-75

As the new generation of warming technology, we introduce our first series of intelligent textiles: j-NOVA intelligent warming textiles.

The intelligent textiles are based on complex nano-technology, and maintain a constant temperature whilst preserving a low energy conversion rate. The technology can achieve an efficiency level of up to 90%, depending on its power source.

The combination of advanced nano material and intelligent modules bring warmth from the fabric and garment itself, which can be scrunched up or washed without affecting its function.

j-NOVA.WORKS aims to balance technology with tradition, and to improve the relationship between nature and humans.

Acanthurus GmbH is the sole European Distributor.

So, j-NOVA is the company with the nanotechnology and Acanthurus represents their interests in Europe. I wish I could find out more about the technology but this is the best I’ve been able to accomplish in the time I have available.

Brain stuff: quantum entanglement and a multi-dimensional universe

I have two brain news bits, one about neural networks and quantum entanglement and another about how the brain operates on more than three dimensions.

Quantum entanglement and neural networks

A June 13, 2017 news item on phys.org describes how machine learning can be used to solve problems in physics (Note: Links have been removed),

Machine learning, the field that’s driving a revolution in artificial intelligence, has cemented its role in modern technology. Its tools and techniques have led to rapid improvements in everything from self-driving cars and speech recognition to the digital mastery of an ancient board game.

Now, physicists are beginning to use machine learning tools to tackle a different kind of problem, one at the heart of quantum physics. In a paper published recently in Physical Review X, researchers from JQI [Joint Quantum Institute] and the Condensed Matter Theory Center (CMTC) at the University of Maryland showed that certain neural networks—abstract webs that pass information from node to node like neurons in the brain—can succinctly describe wide swathes of quantum systems.

An artist’s rendering of a neural network with two layers. At the top is a real quantum system, like atoms in an optical lattice. Below is a network of hidden neurons that capture their interactions (Credit: E. Edwards/JQI)

A June 12, 2017 JQI news release by Chris Cesare, which originated the news item, describes how neural networks can represent quantum entanglement,

Dongling Deng, a JQI Postdoctoral Fellow who is a member of CMTC and the paper’s first author, says that researchers who use computers to study quantum systems might benefit from the simple descriptions that neural networks provide. “If we want to numerically tackle some quantum problem,” Deng says, “we first need to find an efficient representation.”

On paper and, more importantly, on computers, physicists have many ways of representing quantum systems. Typically these representations comprise lists of numbers describing the likelihood that a system will be found in different quantum states. But it becomes difficult to extract properties or predictions from a digital description as the number of quantum particles grows, and the prevailing wisdom has been that entanglement—an exotic quantum connection between particles—plays a key role in thwarting simple representations.

The neural networks used by Deng and his collaborators—CMTC Director and JQI Fellow Sankar Das Sarma and Fudan University physicist and former JQI Postdoctoral Fellow Xiaopeng Li—can efficiently represent quantum systems that harbor lots of entanglement, a surprising improvement over prior methods.

What’s more, the new results go beyond mere representation. “This research is unique in that it does not just provide an efficient representation of highly entangled quantum states,” Das Sarma says. “It is a new way of solving intractable, interacting quantum many-body problems that uses machine learning tools to find exact solutions.”

Neural networks and their accompanying learning techniques powered AlphaGo, the computer program that beat some of the world’s best Go players last year (link is external) (and the top player this year (link is external)). The news excited Deng, an avid fan of the board game. Last year, around the same time as AlphaGo’s triumphs, a paper appeared that introduced the idea of using neural networks to represent quantum states (link is external), although it gave no indication of exactly how wide the tool’s reach might be. “We immediately recognized that this should be a very important paper,” Deng says, “so we put all our energy and time into studying the problem more.”

The result was a more complete account of the capabilities of certain neural networks to represent quantum states. In particular, the team studied neural networks that use two distinct groups of neurons. The first group, called the visible neurons, represents real quantum particles, like atoms in an optical lattice or ions in a chain. To account for interactions between particles, the researchers employed a second group of neurons—the hidden neurons—which link up with visible neurons. These links capture the physical interactions between real particles, and as long as the number of connections stays relatively small, the neural network description remains simple.

Specifying a number for each connection and mathematically forgetting the hidden neurons can produce a compact representation of many interesting quantum states, including states with topological characteristics and some with surprising amounts of entanglement.

Beyond its potential as a tool in numerical simulations, the new framework allowed Deng and collaborators to prove some mathematical facts about the families of quantum states represented by neural networks. For instance, neural networks with only short-range interactions—those in which each hidden neuron is only connected to a small cluster of visible neurons—have a strict limit on their total entanglement. This technical result, known as an area law, is a research pursuit of many condensed matter physicists.

These neural networks can’t capture everything, though. “They are a very restricted regime,” Deng says, adding that they don’t offer an efficient universal representation. If they did, they could be used to simulate a quantum computer with an ordinary computer, something physicists and computer scientists think is very unlikely. Still, the collection of states that they do represent efficiently, and the overlap of that collection with other representation methods, is an open problem that Deng says is ripe for further exploration.

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

Quantum Entanglement in Neural Network States by Dong-Ling Deng, Xiaopeng Li, and S. Das Sarma. Phys. Rev. X 7, 021021 – Published 11 May 2017

This paper is open access.

Blue Brain and the multidimensional universe

Blue Brain is a Swiss government brain research initiative which officially came to life in 2006 although the initial agreement between the École Politechnique Fédérale de Lausanne (EPFL) and IBM was signed in 2005 (according to the project’s Timeline page). Moving on, the project’s latest research reveals something astounding (from a June 12, 2017 Frontiers Publishing press release on EurekAlert),

For most people, it is a stretch of the imagination to understand the world in four dimensions but a new study has discovered structures in the brain with up to eleven dimensions – ground-breaking work that is beginning to reveal the brain’s deepest architectural secrets.

Using algebraic topology in a way that it has never been used before in neuroscience, a team from the Blue Brain Project has uncovered a universe of multi-dimensional geometrical structures and spaces within the networks of the brain.

The research, published today in Frontiers in Computational Neuroscience, shows that these structures arise when a group of neurons forms a clique: each neuron connects to every other neuron in the group in a very specific way that generates a precise geometric object. The more neurons there are in a clique, the higher the dimension of the geometric object.

“We found a world that we had never imagined,” says neuroscientist Henry Markram, director of Blue Brain Project and professor at the EPFL in Lausanne, Switzerland, “there are tens of millions of these objects even in a small speck of the brain, up through seven dimensions. In some networks, we even found structures with up to eleven dimensions.”

Markram suggests this may explain why it has been so hard to understand the brain. “The mathematics usually applied to study networks cannot detect the high-dimensional structures and spaces that we now see clearly.”

If 4D worlds stretch our imagination, worlds with 5, 6 or more dimensions are too complex for most of us to comprehend. This is where algebraic topology comes in: a branch of mathematics that can describe systems with any number of dimensions. The mathematicians who brought algebraic topology to the study of brain networks in the Blue Brain Project were Kathryn Hess from EPFL and Ran Levi from Aberdeen University.

“Algebraic topology is like a telescope and microscope at the same time. It can zoom into networks to find hidden structures – the trees in the forest – and see the empty spaces – the clearings – all at the same time,” explains Hess.

In 2015, Blue Brain published the first digital copy of a piece of the neocortex – the most evolved part of the brain and the seat of our sensations, actions, and consciousness. In this latest research, using algebraic topology, multiple tests were performed on the virtual brain tissue to show that the multi-dimensional brain structures discovered could never be produced by chance. Experiments were then performed on real brain tissue in the Blue Brain’s wet lab in Lausanne confirming that the earlier discoveries in the virtual tissue are biologically relevant and also suggesting that the brain constantly rewires during development to build a network with as many high-dimensional structures as possible.

When the researchers presented the virtual brain tissue with a stimulus, cliques of progressively higher dimensions assembled momentarily to enclose high-dimensional holes, that the researchers refer to as cavities. “The appearance of high-dimensional cavities when the brain is processing information means that the neurons in the network react to stimuli in an extremely organized manner,” says Levi. “It is as if the brain reacts to a stimulus by building then razing a tower of multi-dimensional blocks, starting with rods (1D), then planks (2D), then cubes (3D), and then more complex geometries with 4D, 5D, etc. The progression of activity through the brain resembles a multi-dimensional sandcastle that materializes out of the sand and then disintegrates.”

The big question these researchers are asking now is whether the intricacy of tasks we can perform depends on the complexity of the multi-dimensional “sandcastles” the brain can build. Neuroscience has also been struggling to find where the brain stores its memories. “They may be ‘hiding’ in high-dimensional cavities,” Markram speculates.

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About Blue Brain

The aim of the Blue Brain Project, a Swiss brain initiative founded and directed by Professor Henry Markram, is to build accurate, biologically detailed digital reconstructions and simulations of the rodent brain, and ultimately, the human brain. The supercomputer-based reconstructions and simulations built by Blue Brain offer a radically new approach for understanding the multilevel structure and function of the brain. http://bluebrain.epfl.ch

About Frontiers

Frontiers is a leading community-driven open-access publisher. By taking publishing entirely online, we drive innovation with new technologies to make peer review more efficient and transparent. We provide impact metrics for articles and researchers, and merge open access publishing with a research network platform – Loop – to catalyse research dissemination, and popularize research to the public, including children. Our goal is to increase the reach and impact of research articles and their authors. Frontiers has received the ALPSP Gold Award for Innovation in Publishing in 2014. http://www.frontiersin.org.

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

Cliques of Neurons Bound into Cavities Provide a Missing Link between Structure and Function by Michael W. Reimann, Max Nolte, Martina Scolamiero, Katharine Turner, Rodrigo Perin, Giuseppe Chindemi, Paweł Dłotko, Ran Levi, Kathryn Hess, and Henry Markram. Front. Comput. Neurosci., 12 June 2017 | https://doi.org/10.3389/fncom.2017.00048

This paper is open access.