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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

Preserving heritage smells (scents)

Preserving a smell? It’s an intriguing idea and forms the research focus for scientists at the University College London’s (UCL) Institute for Sustainable Heritage according to an April 6, 2017 Biomed Central news release on EurekAlert,

A ‘Historic Book Odour Wheel’ which has been developed to document and archive the aroma associated with old books, is being presented in a study in the open access journal Heritage Science. Researchers at UCL Institute for Sustainable Heritage created the wheel as part of an experiment in which they asked visitors to St Paul’s Cathedral’s Dean and Chapter library in London to characterize its smell.

The visitors most frequently described the aroma of the library as ‘woody’ (selected by 100% of the visitors who were asked), followed by ‘smoky’ (86%), ‘earthy'(71%) and ‘vanilla’ (41%). The intensity of the smells was assessed as between ‘strong odor’ and ‘very strong odor’. Over 70% of the visitors described the smell as pleasant, 14% as ‘mildly pleasant’ and 14% as ‘neutral’.

In a separate experiment, the researchers presented visitors to the Birmingham Museum and Art Gallery with an unlabelled historic book smell – sampled from a 1928 book they obtained from a second-hand bookshop in London – and collected the terms used to describe the smell. The word ‘chocolate’ – or variations such as ‘cocoa’ or ‘chocolatey’ – was used most often, followed by ‘coffee’, ‘old’, ‘wood’ and ‘burnt’. Participants also mentioned smells including ‘fish’, ‘body odour’, ‘rotten socks’ and ‘mothballs’.

Cecilia Bembibre, heritage scientist at UCL and corresponding author of the study said: “Our odour wheel provides an example of how scientists and historians could begin to identify, analyze and document smells that have cultural significance, such as the aroma of old books in historic libraries. The role of smells in how we perceive heritage has not been systematically explored until now.”

Attempting to answer the question of whether certain smells could be considered part of our cultural heritage and if so how they could be identified, protected and conserved, the researchers also conducted a chemical analysis of volatile organic compounds (VOCs) which they sampled from books in the library. VOCs are chemicals that evaporate at low temperatures, many of which can be perceived as scents or odors.

Combining their findings from the VOC analysis with the visitors’ characterizations, the authors created their Historic Book Odour wheel, which shows the chemical description of a smell (such as acetic acid) together with the sensory descriptions provided by the visitors (such as ‘vinegar’).

Cecilia Bembibre said: “By documenting the words used by the visitors to describe a heritage smell, our study opens a discussion about developing a vocabulary to identify aromas that have cultural meaning and significance.”

She added: “The Historic Book Odour Wheel also has the potential to be used as a diagnostic tool by conservators, informing on the condition of an object, for example its state of decay, through its olfactory profile.”

The authors suggest that, in addition to its use for the identification and conservation of smells, the Historic Book Odour Wheel could potentially be used to recreate smells and aid the design of olfactory experiences in museums, allowing visitors to form a personal connection with exhibits by allowing them to understand what the past smelled like.

Before this can be done, further research is needed to build on the preliminary findings in this study to allow them to inform and benefit heritage management, conservation, visitor experience design and heritage policy making.

Here’s what the Historic Book Odour Wheel looks like,

Odour wheel of historic book containing general aroma categories, sensory descriptors and chemical information on the smells as sampled (colours are arbitrary) Courtesy: Heritage Science [downloaded from https://heritagesciencejournal.springeropen.com/articles/10.1186/s40494-016-0114-1

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

Smell of heritage: a framework for the identification, analysis and archival of historic odours by Cecilia Bembibre and Matija Strlič. Heritage Science20175:2 DOI: 10.1186/s40494-016-0114-1 Published: 7 April 2017

©  The Author(s) 2017

This paper is open access.

Science literacy, science advice, the US Supreme Court, and Britain’s House of Commons

This ‘think’ piece is going to cover a fair bit of ground including science literacy in the general public and in the US Supreme Court, and what that might mean for science advice and UK Members of Parliament (MPs).

Science literacy generally and in the US Supreme Court

A science literacy report for the US National Academy of Sciences (NAS), due sometime from early to mid 2017, is being crafted with an eye to capturing a different perspective according to a March 24, 2016 University of Wisconsin-Madison news release by Terry Dewitt,

What does it mean to be science literate? How science literate is the American public? How do we stack up against other countries? What are the civic implications of a public with limited knowledge of science and how it works? How is science literacy measured?

These and other questions are under the microscope of a 12-member National Academy of Sciences (NAS) panel — including University of Wisconsin—Madison Life Sciences Communication Professor Dominique Brossard and School of Education Professor Noah Feinstein — charged with sorting through the existing data on American science and health literacy and exploring the association between knowledge of science and public perception of and support for science.

The committee — composed of educators, scientists, physicians and social scientists — will take a hard look at the existing data on the state of U.S. science literacy, the questions asked, and the methods used to measure what Americans know and don’t know about science and how that knowledge has changed over time. Critically for science, the panel will explore whether a lack of science literacy is associated with decreased public support for science or research.

Historically, policymakers and leaders in the scientific community have fretted over a perceived lack of knowledge among Americans about science and how it works. A prevailing fear is that an American public unequipped to come to terms with modern science will ultimately have serious economic, security and civic consequences, especially when it comes to addressing complex and nuanced issues like climate change, antibiotic resistance, emerging diseases, environment and energy choices.

While the prevailing wisdom, inspired by past studies, is that Americans don’t stack up well in terms of understanding science, Brossard is not so convinced. Much depends on what kinds of questions are asked, how they are asked, and how the data is analyzed.

It is very easy, she argues, to do bad social science and past studies may have measured the wrong things or otherwise created a perception about the state of U.S. science literacy that may or may not be true.

“How do you conceptualize scientific literacy? What do people need to know? Some argue that scientific literacy may be as simple as an understanding of how science works, the nature of science, [emphasis mine]” Brossard explains. “For others it may be a kind of ‘civic science literacy,’ where people have enough knowledge to be informed and make good decisions in a civics context.”

Science literacy may not be just for the public, it would seem that US Supreme Court judges may not have a basic understanding of how science works. David Bruggeman’s March 24, 2016 posting (on his Pasco Phronesis blog) describes a then current case before the Supreme Court (Justice Antonin Scalia has since died), Note: Links have been removed,

It’s a case concerning aspects of the University of Texas admissions process for undergraduates and the case is seen as a possible means of restricting race-based considerations for admission.  While I think the arguments in the case will likely revolve around factors far removed from science and or technology, there were comments raised by two Justices that struck a nerve with many scientists and engineers.

Both Justice Antonin Scalia and Chief Justice John Roberts raised questions about the validity of having diversity where science and scientists are concerned [emphasis mine].  Justice Scalia seemed to imply that diversity wasn’t esential for the University of Texas as most African-American scientists didn’t come from schools at the level of the University of Texas (considered the best university in Texas).  Chief Justice Roberts was a bit more plain about not understanding the benefits of diversity.  He stated, “What unique perspective does a black student bring to a class in physics?”

To that end, Dr. S. James Gates, theoretical physicist at the University of Maryland, and member of the President’s Council of Advisers on Science and Technology (and commercial actor) has an editorial in the March 25 [2016] issue of Science explaining that the value of having diversity in science does not accrue *just* to those who are underrepresented.

Dr. Gates relates his personal experience as a researcher and teacher of how people’s background inform their practice of science, and that two different people may use the same scientific method, but think about the problem differently.

I’m guessing that both Scalia and Roberts and possibly others believe that science is the discovery and accumulation of facts. In this worldview science facts such as gravity are waiting for discovery and formulation into a ‘law’. They do not recognize that most science is a collection of beliefs and may be influenced by personal beliefs. For example, we believe we’ve proved the existence of the Higgs boson but no one associated with the research has ever stated unequivocally that it exists.

For judges who are under the impression that scientific facts are out there somewhere waiting to be discovered diversity must seem irrelevant. It is not. Who you are affects the questions you ask and how you approach science. The easiest example is to look at how women were viewed when they were subjects in medical research. The fact that women’s physiology is significantly different (and not just in child-bearing ways) was never considered relevant when reporting results. Today, researchers consider not only gender, but age (to some extent), ethnicity, and more when examining results. It’s still not a perfect but it was a step forward.

So when Brossard included “… an understanding of how science works, the nature of science …” as an aspect of science literacy, the judges seemed to present a good example of how not understanding science can have a major impact on how others live.

I’d almost forgotten this science literacy piece as I’d started the draft some months ago but then I spotted a news item about a science advice/MP ‘dating’ service in the UK.

Science advice and UK MPs

First, the news, then, the speculation (from a June 6, 2016 news item on ScienceDaily),

MPs have expressed an overwhelming willingness to use a proposed new service to swiftly link them with academics in relevant areas to help ensure policy is based on the latest evidence.

A June 6, 2016 University of Exeter press release, which originated the news item, provides more detail about the proposed service and the research providing the supporting evidence (Note: A link has been removed),

The government is pursuing a drive towards evidence-based policy, yet policy makers still struggle to incorporate evidence into their decisions. One reason for this is limited easy access to the latest research findings or to academic experts who can respond to questions about evidence quickly.

Researchers at Cardiff University, the University of Exeter and University College London have today published results of the largest study to date reporting MPs’ attitudes to evidence in policy making and their reactions to a proposed Evidence Information Service (EIS) – a rapid match-making advisory service that would work alongside existing systems to put MPs in touch with relevant academic experts.

Dr Natalia Lawrence, of the University of Exeter, said: “It’s clear from our study that politicians want to ensure their decisions incorporate the most reliable evidence, but it can sometimes be very difficult for them to know how to access the latest research findings. This new matchmaking service could be a quick and easy way for them to seek advice from cutting-edge researchers and to check their understanding and facts. It could provide a useful complement to existing highly-valued information services.”

The research, published today in the journal Evidence and Policy, reports the findings of a national consultation exercise between politicians and the public. The researchers recruited members of the public to interview their local parliamentary representative. In total 86, politicians were contacted with 56 interviews completed. The MPs indicated an overwhelming willingness to use a service such as the EIS, with 85% supporting the idea, but noted a number of potential reservations related to the logistics of the EIS such as response time and familiarity with the service. Yet, the MPs indicated that their logistical reservations could be overcome by accessing the EIS via existing highly-valued parliamentary information services such as those provided by the House of Commons and Lords Libraries. Furthermore prior to rolling out the EIS on a nationwide basis it would first need to be piloted.

Developing the proposed EIS in line with feedback from this consultation of MPs would offer the potential to provide policy makers with rapid, reliable and confidential evidence from willing volunteers from the research community.

Professor Chris Chambers, of Cardiff University, said: “The government has given a robust steer that MPs need to link in more with academics to ensure decisions shaping the future of the country are evidence-based. It’s heartening to see that there is a will to adopt this system and we now need to move into a phase of developing a service that is both simple and effective to meet this need.”

The next steps for the project are parallel consultations of academics and members of the public and a pilot of the EIS, using funding from GW4 alliance of universities, made up of Bath, Bristol, Cardiff and Exeter.

What this study shows:
• The consultation shows that politicians recognise the importance of evidence-based policy making and agree on the need for an easier and more direct linkage between academic experts and policy makers.
• Politicians would welcome the creation of the EIS as a provider of rapid, reliable and confidential evidence.

What this study does not show:
• This study does not show how academics would provide evidence. This was a small-scale study which consulted politicians and has not attempted to give voice to the academic community.
• This study does not detail the mechanism of an operational EIS. Instead it indicates the need for a service such as the EIS and suggests ways in which the EIS can be operationalized.

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

Service as a new platform for supporting evidence-based policy: a consultation of UK parliamentarians by Natalia Lawrence, Jemma Chambers, Sinead Morrison, Sven Bestmann, Gerard O’Grady, Christopher Chambers, Andrew Kythreotis. Evidence & Policy: A Journal of Research, Debate and Practice DOI: http://dx.doi.org/10.1332/174426416X14643531912169 Appeared or available online: June 6, 2016

This paper is behind a paywall open access. *Corrected June 17, 2016.*

It’s an interesting idea and I can understand the appeal. However, operationalizing this ‘dating’ or ‘matchmaking’ service could prove quite complex. I appreciate the logistics issues but I’m a little more concerned about the MPs’ science literacy. Are they going to be like the two US justices who believe that science is the pursuit of immutable facts? What happens if two MPs are matched up with a different scientist and those two scientists didn’t agree about what the evidence says. Or, what happens if one scientist is more cautious than the other. There are all kinds of pitfalls. I’m not arguing against the idea but it’s going to require a lot of careful consideration.

Drone fly larvae avoid bacterial contamination due to their nanopillars

This is some fascinating bug research. From an April 6, 2016 news item on phys.org,

The immature stage of the drone fly (Eristalis tenax) is known as a “rat-tailed maggot” because it resembles a hairless baby rodent with a “tail” that is actually used as a breathing tube. Rat-tailed maggots are known to live in stagnant, fetid water that is rich in bacteria, fungi, and algae. However, despite this dirty environment, they are able to avoid infection by these microorganisms.

An April 6, 2016 Entomological Society of America news release on EurekAlert, which originated the news item, describes the findings,

Recently, Matthew Hayes, a cell biologist at the Institute of Ophthalmology at University College London in England, discovered never-before-seen structures that appear to keep the maggot mostly free of bacteria, despite living where microorganisms flourish. …

With scanning and transmission electron microscopes, Hayes carefully examined the larva and saw that much of its body is covered with thin spines, or “nanopillars,” that narrow to sharp points. Once he confirmed the spiky structures were indeed part of the maggot, he noticed a direct relationship between the presence of the spines and the absence of bacteria on the surface of the larva. He speculated that the carpet of spines simply makes it impossible for the bacteria to find enough room to adhere to the larva’s body surface.

Here’s an image of the nanopillars,

Caption: This electron-microscope image expose the spines, or "nanopillars," that poke up from the body of the rat-tailed maggot. The length and density of the spines vary as shown in this cross-section image of the cuticle. Credit: Matthew Hayes

Caption: This electron-microscope image expose the spines, or “nanopillars,” that poke up from the body of the rat-tailed maggot. The length and density of the spines vary as shown in this cross-section image of the cuticle. Credit: Matthew Hayes

Back to the news release,

“They’re much like anti-pigeon spikes that keep the birds away because they can’t find a nice surface to land on,” he said.

Hayes also ventured that the spines could possibly have superoleophobic properties (the ability to repel oils), which would also impede the bacteria from colonizing and forming a biofilm that could ultimately harm or kill the maggot. The composition of the spines is as unique as the structures themselves, Hayes said. Each spine appears to consist of a stack of hollow-cored disks, the largest at the bottom and the smallest at the top.

“What I really think they look like is the baby’s toy with the stack of rings of decreasing size, but on a very small scale,” he said. “I’ve worked in many different fields and looked at lots of different things, and I’ve never seen anything that looks like it.”

This work with the rat-tailed maggot is leading him to examine other insects as well, including the ability of another aquatic invertebrate — the mosquito larva — to thwart bacteria. Such antibacterial properties have applications in many different fields, including ophthalmology and other medical fields where biofilms can foul surgical instruments or implanted devices.

For now, though, he’s thrilled about shedding light on the underappreciated rat-tailed maggot and revealing its spiny armor.

“I’ve loved insects since I was a child, when I would breed butterflies and moths,” he said. “I’m just so chuffed to have discovered something a bit new about insects!”

I am charmed by Hayes’s admission of being “chuffed.”

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

Identification of Nanopillars on the Cuticle of the Aquatic Larvae of the Drone Fly (Diptera: Syrphidae) by Matthew J. Hayes, Timothy P. Levine, Roger H. Wilson. DOI: http://dx.doi.org/10.1093/jisesa/iew019 36 First published online: 30 March 2016

This is an open access paper.

Observing silica microspheres leads to theories about schools of fish and human crowds

Researchers developing theories about the crowd behaviour of tiny particles believe the theories may have some relevance to macro world phenomena.

[downloaded from http://www.ucl.ac.uk/news/news-articles/0316/090316-crowd-control]

[downloaded from http://www.ucl.ac.uk/news/news-articles/0316/090316-crowd-control]

From a March 9, 2016 news item on Nanowerk,

Crowds formed from tiny particles disperse as their environment becomes more disordered, according to scientists from UCL [University College London, UK], Bilkent University [Turkey] and Université Pierre et Marie Curie [France].

The new mechanism is counterintuitive and might help describe crowd behaviour in natural, real-world systems where many factors impact on individuals’ responses to either gather or disperse.

“Bacterial colonies, schools of fish, flocking birds, swarming insects and pedestrian flow all show collective and dynamic behaviours which are sensitive to changes in the surrounding environment and their dispersal or gathering can be sometimes the difference between life and death,” said lead researcher, Dr Giorgio Volpe, UCL Chemistry.

A March 9, 2016 UCL press release (also on EurekAlert), which originated the news item, expands on the theme,

“The crowd often has different behaviours to the individuals within it and we don’t know what the simple rules of motion are for this. If we understood these and how they are adapted in complex environments, we could externally regulate active systems. Examples include controlling the delivery of biotherapeutics in nanoparticle carriers to the target in the body, or improving crowd security in a panic situation.”

The study, published today in Nature Communications, investigated the behaviour of active colloidal particles in a controllable system to find out the rules of motion for individuals gathering or dispersing in response to external factors.

Colloidal particles are free to diffuse through a solution and for this study suspended silica microspheres were used. The colloidal particles became active with the addition of E. coli bacteria to the solution. Active colloidal particles were chosen as a model system because they move of their own accord using the energy from their environment, which is similar to how animals move to get food.

Initially, the active colloidal particles gathered at the centre of the area illuminated by a smooth beam which provided an active potential. Disorder was introduced using a speckle beam pattern which disordered the attractive potential and caused the colloids to disperse from the area at a rate of 0.6 particles per minute over 30 minutes. The particles switched between gathering and dispersing proportional to the level of external disorder imposed.

Erçağ Pinçe, who is first author of the study with Dr Sabareesh K. P. Velu, both Bilkent University, said: “We didn’t expect to see this mechanism as it’s counterintuitive but it might already be at play in natural systems. Our finding suggests there may be a way to control active matter through external factors. We could use it to control an existing system, or to design active agents that exploit the features of the environment to perform a given task, for example designing distinct depolluting agents for different types of polluted terrains and soils.”

Co-author, Dr Giovanni Volpe, Bilkent University, added: “Classical statistical physics allows us to understand what happens when a system is at equilibrium but unfortunately for researchers, life happens far from equilibrium. Behaviours are often unpredictable as they strongly depend on the characteristic of the environment. We hope that understanding these behaviours will help reveal the physics behind living organisms, but also help deliver innovative technologies in personalised healthcare, environmental sustainability and security.”

The team now plan on applying their findings to real-life situations to improve society. In particular, they want to exploit the main conclusions from their work to develop intelligent nanorobots for applications in drug-delivery and environmental sustainability that are capable of efficiently navigate through complex natural environments.

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

Disorder-mediated crowd control in an active matter system by Erçağ Pinçe, Sabareesh K. P. Velu, Agnese Callegari, Parviz Elahi, Sylvain Gigan, Giovanni Volpe, & Giorgio Volpe. Nature Communications 7, Article number: 10907 doi:10.1038/ncomms10907 Published 09 March 2016

This is an open access paper.

Revolutionary ‘smart’ windows from the UK

This is the first time I’ve seen self-cleaning and temperature control features mentioned together with regard to a ‘smart’ window, which makes this very exciting news. From a Jan. 20, 2016 UK Engineering and Physical Sciences Research Council (EPSRC) press release (also on EurekAlert),

A revolutionary new type of smart window could cut window-cleaning costs in tall buildings while reducing heating bills and boosting worker productivity. Developed by University College London (UCL) with support from EPSRC, prototype samples confirm that the glass can deliver three key benefits:

Self-cleaning: The window is ultra-resistant to water, so rain hitting the outside forms spherical droplets that roll easily over the surface – picking up dirt, dust and other contaminants and carrying them away. This is due to the pencil-like, conical design of nanostructures engraved onto the glass, trapping air and ensuring only a tiny amount of water comes into contact with the surface. This is different from normal glass, where raindrops cling to the surface, slide down more slowly and leave marks behind.
Energy-saving: The glass is coated with a very thin (5-10nm) film of vanadium dioxide which during cold periods stops thermal radiation escaping and so prevents heat loss; during hot periods it prevents infrared radiation from the sun entering the building. Vanadium dioxide is a cheap and abundant material, combining with the thinness of the coating to offer real cost and sustainability advantages over silver/gold-based and other coatings used by current energy-saving windows.
Anti-glare: The design of the nanostructures also gives the windows the same anti-reflective properties found in the eyes of moths and other creatures that have evolved to hide from predators. It cuts the amount of light reflected internally in a room to less than 5 per cent – compared with the 20-30 per cent achieved by other prototype vanadium dioxide coated, energy-saving windows – with this reduction in ‘glare’ providing a big boost to occupant comfort.

This is the first time that a nanostructure has been combined with a thermochromic coating. The bio-inspired nanostructure amplifies the thermochromics properties of the coating and the net result is a self-cleaning, highly performing smart window, said Dr Ioannis Papakonstantinou of UCL.

The UCL team calculate that the windows could result in a reduction in heating bills of up to 40 per cent, with the precise amount in any particular case depending on the exact latitude of the building where they are incorporated. Windows made of the ground-breaking glass could be especially well-suited to use in high-rise office buildings.

Dr Ioannis Papakonstantinou of UCL, project leader, explains: It’s currently estimated that, because of the obvious difficulties involved, the cost of cleaning a skyscraper’s windows in its first 5 years is the same as the original cost of installing them. Our glass could drastically cut this expenditure, quite apart from the appeal of lower energy bills and improved occupant productivity thanks to less glare. As the trend in architecture continues towards the inclusion of more glass, it’s vital that windows are as low-maintenance as possible.

So, when can I buy these windows? (from the press release; Note: Links have been removed)

Discussions are now under way with UK glass manufacturers with a view to driving this new window concept towards commercialisation. The key is to develop ways of scaling up the nano-manufacturing methods that the UCL team have specially developed to produce the glass, as well as scaling up the vanadium dioxide coating process. Smart windows could begin to reach the market within around 3-5 years [emphasis mine], depending on the team’s success in securing industrial interest.

Dr Papakonstantinou says: We also hope to develop a ‘smart’ film that incorporates our nanostructures and can easily be added to conventional domestic, office, factory and other windows on a DIY [do-it-yourself] basis to deliver the triple benefit of lower energy use, less light reflection and self-cleaning, without significantly affecting aesthetics.

Professor Philip Nelson, Chief Executive of EPSRC said: This project is an example of how investing in excellent research drives innovation to produce tangible benefits. In this case the new technique could deliver both energy savings and cost reductions.

A 5-year European Research Council (ERC) starting grant (IntelGlazing) has been awarded to fabricate smart windows on a large scale and test them under realistic, outdoor environmental conditions.

The UCL team that developed the prototype smart window includes Mr Alaric Taylor, a PhD student in Dr Papakonstantinou’s group, and Professor Ivan Parkin from UCL’s Department of Chemistry.

I wish them good luck.

One last note, these new windows are the outcome of a 2.5 year EPSRC funded project: Biologically Inspired Nanostructures for Smart Windows with Antireflection and Self-Cleaning Properties, which ended in Sept.  2015.

Using quantum dots to detect and identify explosives

This research is courtesy of the University College London (UCL) according to a Dec. 9, 2015 news item on Nanowerk,

A new test for detecting multiple explosives simultaneously has been developed by UCL scientists. The proof-of-concept sensor is designed to quickly identify and quantify five commonly used explosives in solution to help track toxic contamination in waste water and improve the safety of public spaces.

Lead researcher, Dr William Peveler (UCL Chemistry), said: “This is the first time multiple explosives have been detected using a single sensor before, demonstrating proof-of-concept for this approach. Our sensor changes colour within 10 seconds to give information about how much and what explosives are present in a sample. Following further development, we hope it will be used to quickly analyse the nature of threats and inform tailored responses.”

A Dec. 9, 2015 UCL press release (also on EurekAlert), which originated the news item, expands on the theme,

Dr Peveler, added: “We analysed explosives which are commonly used for industrial and military purposes to create a useful tool for environmental and security monitoring. For example, DNT is a breakdown product from landmines, and RDX and PETN have been used in terror plots in recent years as they can be hard to detect using sniffer dogs. Our test can quickly identify these compounds so we see it having a variety of applications from monitoring the waste water of munitions factories and military ranges to finding evidence of illicit activities.”

The sensor is made of quantum dots, which are tiny light-emitting particles or nanomaterials, to which explosive targeting receptors are attached. As each explosive binds to the quantum dot, it quenches the light being emitted to a different degree. The distinct changes in colour are analysed computationally in a variety of conditions to give a unique fingerprint for each compound, allowing multiple explosives to be detected with a single test.

Senior author, Professor Ivan Parkin (UCL Chemistry), said: “Our sensor is a significant step forward for multiple explosives detection. Current methods can be laborious and require expensive equipment but our test is designed to be inexpensive, fast and use a much smaller volume of sample than previously possible. Although all of these factors are important, speed and accuracy are crucial when identifying explosive compounds.”

The team plan to take it from the laboratory into the field by blind testing it with contaminated waste water samples. They also hope to improve the sensitivity of the test by tailoring the surfaces of the quantum dots. Currently, its limit is less than one part per million which the team hope to increase into the part per billion range.

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

Multichannel Detection and Differentiation of Explosives with a Quantum Dot Array by William J. Peveler, Alberto Roldan, Nathan Hollingsworth, Michael J. Porte‡, and Ivan P. Parkin. ACS Nano, Article ASAP DOI: 10.1021/acsnano.5b06433 Publication Date (Web): November 18, 2015

Copyright © 2015 American Chemical Society

This paper is behind a paywall.

Using scientific methods and technology to explore living systems as artistic subjects: bioart

There is a fascinating set of stories about bioart designed to whet your appetite for more (*) in a Nov. 23, 2015 Cell Press news release on EurekAlert (Note: A link has been removed),

Joe Davis is an artist who works not only with paints or pastels, but also with genes and bacteria. In 1986, he collaborated with geneticist Dan Boyd to encode a symbol for life and femininity into an E. coli bacterium. The piece, called Microvenus, was the first artwork to use the tools and techniques of molecular biology. Since then, bioart has become one of several contemporary art forms (including reclamation art and nanoart) that apply scientific methods and technology to explore living systems as artistic subjects. A review of the field, published November 23, can be found in Trends in Biotechnology.

Bioart ranges from bacterial manipulation to glowing rabbits, cellular sculptures, and–in the case of Australian-British artist Nina Sellars–documentation of an ear prosthetic that was implanted onto fellow artist Stelarc’s arm. In the pursuit of creating art, practitioners have generated tools and techniques that have aided researchers, while sometimes crossing into controversy, such as by releasing invasive species into the environment, blurring the lines between art and modern biology, raising philosophical, societal, and environmental issues that challenge scientific thinking.

“Most people don’t know that bioart exists, but it can enable scientists to produce new ideas and give us opportunities to look differently at problems,” says author Ali K. Yetisen, who works at Harvard Medical School and the Wellman Center for Photomedicine, Massachusetts General Hospital. “At the same time there’s been a lot of ethical and safety concerns happening around bioart and artists who wanted to get involved in the past have made mistakes.”

Here’s a sample of Joe Davis’s work,

 Caption This photograph shows polyptich paintings by Joe Davis of his 28-mer Microvenus DNA molecule (2006 Exhibition in Greece at Athens School of Fine Arts). Credit: Courtesy of Joe Davis

This photograph shows polyptich paintings by Joe Davis of his 28-mer Microvenus DNA molecule (2006 Exhibition in Greece at Athens School of Fine Arts). Credit: Courtesy of Joe Davis

The news release goes on to recount a brief history of bioart, which stretches back to 1928 and then further back into the 19th and 18th centuries,

In between experiments, Alexander Fleming would paint stick figures and landscapes on paper and in Petri dishes using bacteria. In 1928, after taking a brief hiatus from the lab, he noticed that portions of his “germ paintings,” had been killed. The culprit was a fungus, penicillin–a discovery that would revolutionize medicine for decades to come.

In 1938, photographer Edward Steichen used a chemical to genetically alter and produce interesting variations in flowering delphiniums. This chemical, colchicine, would later be used by horticulturalists to produce desirable mutations in crops and ornamental plants.

In the late 18th and early 19th centuries, the arts and sciences moved away from traditionally shared interests and formed secular divisions that persisted well into the 20th century. “Appearance of environmental art in the 1970s brought about renewed awareness of special relationships between art and the natural world,” Yetisen says.

To demonstrate how we change landscapes, American sculptor Robert Smithsonian paved a hillside with asphalt, while Bulgarian artist Christo Javacheffa (of Christo and Jeanne-Claude) surrounded resurfaced barrier islands with bright pink plastic.

These pieces could sometimes be destructive, however, such as in Ten Turtles Set Free by German-born Hans Haacke. To draw attention to the excesses of the pet trade, he released what he thought were endangered tortoises back to their natural habitat in France, but he inadvertently released the wrong subspecies, thus compromising the genetic lineages of the endangered tortoises as the two varieties began to mate.

By the late 1900s, technological advances began to draw artists’ attention to biology, and by the 2000s, it began to take shape as an artistic identity. Following Joe Davis’ transgenic Microvenus came a miniaturized leather jacket made of skin cells, part of the Tissue Culture & Art Project (initiated in 1996) by duo Oran Catts and Ionat Zurr. Other examples of bioart include: the use of mutant cacti to simulate appearance of human hair in the place of cactus spines by Laura Cinti of University College London’s C-Lab; modification of butterfly wings for artistic purposes by Marta de Menezes of Portugal; and photographs of amphibian deformation by American Brandon Ballengée.

“Bioart encourages discussions about societal, philosophical, and environmental issues and can help enhance public understanding of advances in biotechnology and genetic engineering,” says co-author Ahmet F. Coskun, who works in the Division of Chemistry and Chemical Engineering at California Institute of Technology.

Life as a Bioartist

Today, Joe Davis is a research affiliate at MIT Biology and “Artist-Scientist” at the George Church Laboratory at Harvard–a place that fosters creativity and technological development around genetic engineering and synthetic biology. “It’s Oz, pure and simple,” Davis says. “The total amount of resources in this environment and the minds that are accessible, it’s like I come to the city of Oz every day.”

But it’s not a one-way street. “My particular lab depends on thinking outside the box and not dismissing things because they sound like science fiction,” says [George M.] Church, who is also part of the Wyss Institute for Biologically Inspired Engineering. “Joe is terrific at keeping us flexible and nimble in that regard.”

For example, Davis is working with several members of the Church lab to perform metagenomics analyses of the dust that accumulates at the bottom of money-counting machines. Another project involves genetically engineering silk worms to spin metallic gold–an homage to the fairy tale of Rumpelstiltskin.

“I collaborate with many colleagues on projects that don’t necessarily have direct scientific results, but they’re excited to pursue these avenues of inquiry that they might not or would not look into ordinarily–they might try to hide it, but a lot of scientists have poetic souls,” Davis says. “Art, like science, has to describe the whole word and you can’t describe something you’re basically clueless about. The most exciting part of these activities is satiating overwhelming curiosity about everything around you.”

The number of bioartists is still small, Davis says, partly because of a lack of federal funding of the arts in general. Accessibility to the types of equipment bioartists want to experiment with can also be an issue. While Davis has partnered with labs over the past few decades, other artists affiliate themselves with community access laboratories that are run by do-it-yourself biologists. One way that universities can help is to create departmental-wide positions for bioartists to collaborate with scientists.

“In the past, there have been artists affiliated with departments in a very utilitarian way to produce figures or illustrations,” Church says. “Having someone like Joe stimulates our lab to come together in new ways and if we had more bioartists, I think thinking out of the box would be a more common thing.”

“In the era of genetic engineering, bioart will gain new meanings and annotations in social and scientific contexts,” says Yetisen. “Bioartists will surely take up new roles in science laboratories, but this will be subject to ethical criticism and controversy as a matter of course.”

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

Bioart by Ali K. Yetisen, Joe Davis, Ahmet F. Coskun, George M. Church, Seok Hyun. Trends in Biotechnology,  DOI: http://dx.doi.org/10.1016/j.tibtech.2015.09.011 Published Online: November 23, 2015

This paper appears to be open access.

*Removed the word ‘featured’ on Dec. 1, 2015 at 1030 hours PDT.