Tag Archives: Ed Yong

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

Political internship (Canada’s Liberal Party)

i don’t usually feature jobs for political parties but there appears to be a movement afoot in the US where scientists are possibly going to run for political office so it seems more à propos than usual. Before getting to the job information (for a Canadian political party), here’s more about the nascent scientists as politicians movement from a Jan. 25, 2017 article (Professor Smith Goes to Washington) by Ed Yong for The Atlantic (Note: Links have been removed),

For American science, the next four years look to be challenging. The newly inaugurated President Trump, and many of his Cabinet picks, have repeatedly cast doubt upon the reality of human-made climate change, questioned the repeatedly proven safety of vaccines. Since the inauguration, the administration has already frozen grants and contracts by the Environmental Protection Agency and gagged researchers at the US Department of Agriculture. Many scientists are asking themselves: What can I do?

And the answer from a newly formed group called 314 Action is: Get elected.

The organization, named after the first three digits of pi, is a political action committee that was created to support scientists in running for office. It’s the science version of Emily’s List, which focuses on pro-choice female candidates, or VoteVets, which backs war veterans. “A lot of scientists traditionally feel that science is above politics but we’re seeing that politics is not above getting involved in science,” says founder Shaughnessy Naughton. “We’re losing, and the only way to stop that is to get more people with scientific backgrounds at the table.”

Yong is a good writer and the article offers some insight into why scientists do or don’t involve themselves in the political process along with links for more information.

***ETA Feb. 13, 2017: phys.org has published an article by Deborah Netburn (originally written for the Los Angeles Times) which offers some insight into scientists some of whom are involving themselves in politics for the first in their lives in a Feb. 13, 2017 news item titled ‘Science entering a new frontier: Politics‘.***

Science Borealis, the Canadian science blog aggregrator/community, has chimed in on the science and politics situation in the US with two blog postings on the topic. I wish they’d used titles that more accurately reflected the content but there’s Sarah Boon’s Jan. 24, 2017 posting, The War on Science: Can the US Learn From Canada? on her Watershed Moments blog, where she notes how different the situations are and how much Americans have already done and are doing to work on the issues,

When Donald Trump was first elected president of the United States, our editorial team at  Science Borealis talked about whether or not we should write an editorial supporting US scientists in what was likely going to become a fight for science. In the end we decided not to write it, for a number of reasons. For one thing, the likely impact of Trump on science remained a huge unknown. But for another thing, we thought US scientists were already well-prepared for a war on science. …

Unfortunately, Boon goes on to offer a collection of writings on the Canadian situation. I understand it’s well meant but I can’t help recalling people who rushed to comfort me in a difficult situation by recounting their own stories, at length. It wasn’t as helpful as they might have hoped.

John Dupuis’ Jan. 25, 2017 posting, The Trump War on Science: What Can the US Learn From Canada’s Experience? on his Confessions of a Science Librarian blog, is more egregiously titled but he goes on to provide links to resources for more information on the situation in the US. Although he, too, goes on to offer links to more about the Canadian situation.

One final observation, I have an objection to the term ‘war on science’; there was never a war on science in Canada. There was/is a war on certain kinds of science. In any event, here’s getting to the point of this posting.

Internship

For those scientific (stretching past political science students) types who think they might be interested in politics,  from the 2017 Liberal Party of Canada Internship Program page,

Are you a young Canadian with a love of politics? Are you passionate about serving your community, engaging with volunteers, and talking with Canadians about the issues that matter most? The Liberal Party of Canada is looking for hardworking young leaders to join Justin Trudeau’s team this summer, to help us continue to grow Canada’s Liberal movement from coast to coast to coast.

Whether it includes marching in the Vancouver Pride Parade, knocking on doors in Halifax, getting our message out to Canadians using social media, supporting our local Liberal associations in their communities, or learning directly from our campaign experts in Ottawa, an internship with the LPC is guaranteed to be an unforgettable summer! Our interns will have the opportunity to learn the foundations of organizing and campaigning directly from the people who paved our road to victory in 2015, and those who are already hard at work planning for the next election. With less than three years until the next general election, our team is looking for talented young Canadians to bring fresh and innovative ideas to the table.

You’ll gain valuable career experience, and get to know leading members of the Liberal team.

While every individual’s tasks and projects will be different, selected Liberal interns may work in areas including:

  • Communications and Media Relations
  • National Field – Campaigns
  • Social Media
  • Email Marketing
  • Graphic and Web Design
  • Local Field and Outreach
  • Riding Services
  • Party Operations
  • Finance and Accounting

Who: You! All Registered Liberals are encouraged to apply! We are looking for talented young Canadians from coast to coast to coast to work on Justin Trudeau’s team and become the next generation of leaders in the largest, most open, and most inclusive political movement in Canadian history.

Where: Most Interns will be placed in the Liberal Party of Canada National Office in Ottawa, and there also exciting opportunities available in our Regional Offices across the country. Please indicate in your application at least one city where you would be interested in working with our team.

When: Internship positions will run from Monday, May 1 to Friday, August 25. You must be available full-time for the duration of the internship.

This is a full-time, paid internship. [emphasis mine]

All applicants will receive an email of confirmation upon the submission of their application. Interviews will be conducted throughout the month of February. Due to a high volume of applications, only those who are selected for an interview will be contacted.

Apply now

Application Deadline: 11:59pm PST on Friday, February 10, 2017. [emphasis mine]

There is a FAQs (frequently asked questions) section on the the 2017 Liberal Party of Canada Internship Program page. Good luck!

The relationship between Valyrian steel (from Game of Thrones), Damascus steel, and nuclear nanotechnology

There’s a very interesting June 20, 2014 posting by Charles Day on his Dayside blog (located on the Physics Today website). Day manages to relate the Game of Thrones tv series to nuclear power and nanotechnology,

The military technology of A Song of Ice and Fire, George R. R. Martin’s series of fantasy novels, is medieval with an admixture of the supernatural. Dragons aside, among the most prized weapons are swords made from Valyrian steel, which are lighter, stronger, and sharper than ordinary steel swords.

Like many of the features in the rich world of the novels and their TV adaptation, Game of Thrones, Valyrian steel has a historical inspiration. Sometime before 300 BC, metalworkers in Southern India discovered a way to make small cakes of high-carbon steel known as wootz. Thanks to black wavy bands of Fe3C particles that pervade the metal, wootz steel was already strong. …

Perhaps because the properties of wootz and Damascus steels depended, in part, on a particular kind of iron ore, the ability of metallurgists to make the alloys was lost sometime in the 18th century. In A Song of Ice and Fire, the plot plays out during an era in which making Valyrian steel is a long-lost art.

Martin’s knowledge of metallurgy is perhaps shaky. …

Interestingly, the comments on the blog posting largely concern themselves with whether George RR Martin knows anything about metallurgy. The consensus being that he does and that the problems in the Game of Thrones version of metallurgy lie with the series writers.

I first came across the Damascus steel, wootz, and carbon nanotube story in 2008 and provided a concise description on my Nanotech Mysteries wiki Middle Ages page,

Damascus steel blades were first made in the 8th century CE when they acquired a legendary status as unlike other blades they were able to cut through bone and stone while remaining sharp enough to cut a piece of silk. They were also flexible which meant they didn’t break off easily in a sword fight. The secret for making the blades died (history does not record how) about 1700 CE and there hasn’t been a new blade since.

 The blades were generally made from metal ingots prepared in India using special recipes which probably put just the right amount of carbon and other impurities into the iron. By following these recipes and following specific forging techniques craftsmen ended up making nanotubes … When these blades were nearly finished, blacksmiths would etch them with acid. This brought out the wavy light and dark lines that make Damascus swords easy to recognize.3

 It turns out part of the secret to the blade is nanotechnology. Scientists discovered this by looking at a Damascus steel blade from 1700 under an electron microscope. It seems those unknown smiths were somehow encasing cementite nanowires in carbon nanotubes then forging them into the steel blades giving them their legendary strength and flexibility.

The reference information I used then seems to be no longer available online but there is this more than acceptable alternative, a Sept. 27, 2008 postiing by Ed Yong from his Not Exactly Rocket Science blog (on ScienceBlogs.com; Note: A link has been removed),

In medieval times, crusading Christian knights cut a swathe through the Middle East in an attempt to reclaim Jerusalem from the Muslims. The Muslims in turn cut through the invaders using a very special type of sword, which quickly gained a mythical reputation among the Europeans. These ‘Damascus blades‘ were extraordinarily strong, but still flexible enough to bend from hilt to tip. And they were reputedly so sharp that they could cleave a silk scarf floating to the ground, just as readily as a knight’s body.

They were superlative weapons that gave the Muslims a great advantage, and their blacksmiths carefully guarded the secret to their manufacture. The secret eventually died out in the eighteenth century and no European smith was able to fully reproduce their method.

Two years ago, Marianne Reibold and colleagues from the University of Dresden uncovered the extraordinary secret of Damascus steel – carbon nanotubes. The smiths of old were inadvertently using nanotechnology.

Getting back to Day, he goes on to explain the Damascus/Valyrian steel connection to nuclear power (Note: Links have been removed),

Valyrian and Damascus steels were on my mind earlier this week when I attended a session at TechConnect World on the use of nanotechnology in the nuclear power industry.

Scott Anderson of Lockheed Martin gave the introductory talk. Before the Fukushima disaster, Anderson pointed out, the principal materials science challenge in the nuclear industry lay in extending the lifetime of fuel rods. Now the focus has shifted to accident-tolerant fuels and safer, more durable equipment.

Among the other speakers was MIT’s Ju Li, who described his group’s experiments with incorporating carbon nanotubes (CNTs) in aluminum to boost the metal’s resistance to radiation damage. In a reactor core, neutrons and other ionizing particles penetrate vessels, walls, and other structures, where they knock atoms off lattice sites. The cumulative effect of those displacements is to create voids and other defects that weaken the structures.

Li isn’t sure yet how the CNTs resist irradiation and toughen the aluminum, but at the end of his talk he recalled their appearance in another metal, steel.

In 2006 Peter Paufler of Dresden University of Technology and his collaborators used high-resolution transmission electron microscopy (TEM) to examine the physical and chemical microstructure of a sample of Damascus steel from the 17th century.

The saber from which the sample was taken was forged in Isfahan, Persia, by the famed blacksmith Assad Ullah. As part of their experiment, Paufler and his colleagues washed the sample in hydrochloric acid to remove Fe3C particles. A second look with TEM revealed the presence of CNTs.

There’s still active interest in researching Damascus steel blades as not all the secrets behind the blade’s extraordinary qualities have been revealed yet. There is a March 13, 2014 posting here which describes a research project where Chinese researchers are attempting (using computational software) to uncover the reason for the blade’s unique patterns,

It seems that while researchers were able to answer some questions about the blade’s qualities, researchers in China believe they may have answered the question about the blade’s unique patterns, from a March 12, 2014 news release on EurekAlert,

Blacksmiths and metallurgists in the West have been puzzled for centuries as to how the unique patterns on the famous Damascus steel blades were formed. Different mechanisms for the formation of the patterns and many methods for making the swords have been suggested and attempted, but none has produced blades with patterns matching those of the Damascus swords in the museums. The debate over the mechanism of formation of the Damascus patterns is still ongoing today. Using modern metallurgical computational software (Thermo-Calc, Stockholm, Sweden), Professor Haiwen Luo of the Central Iron and Steel Research Institute in Beijing, together with his collaborator, have analyzed the relevant published data relevant to the Damascus blades, and present a new explanation that is different from other proposed mechanisms.

At the time the researchers were hoping to have someone donate a piece of genuine Damascus steel blade. From my March 13, 2014 posting,

Note from the authors: It would be much appreciated if anyone would like to donate a piece of genuine Damascus blade for our research.

Corresponding Author:

LUO Haiwen
Email: haiwenluo@126.com

Perhaps researchers will manage to solve the puzzle of how medieval craftsman were once able to create extraordinary steel blades.

University of Waterloo researchers use 2.5M (virtual) neurons to simulate a brain

I hinted about some related work at the University of Waterloo earlier this week in my Nov. 26, 2012 posting (Existential risk) about a proposed centre at the University of Cambridge which would be tasked with examining possible risks associated with ‘ultra intelligent machines’.  Today (Science (magazine) published an article about SPAUN (Semantic Pointer Architecture Unified Network) [behind a paywall])and its ability to solve simple arithmetic and perform other tasks as well.

Ed Yong writing for Nature magazine (Simulated brain scores top test marks, Nov. 29, 2012) offers this description,

Spaun sees a series of digits: 1 2 3; 5 6 7; 3 4 ?. Its neurons fire, and it calculates the next logical number in the sequence. It scrawls out a 5, in legible if messy writing.

This is an unremarkable feat for a human, but Spaun is actually a simulated brain. It contains2.5 millionvirtual neurons — many fewer than the 86 billion in the average human head, but enough to recognize lists of numbers, do simple arithmetic and solve reasoning problems.

Here’s a video demonstration, from the University of Waterloo’s Nengo Neural Simulator home page,

The University of Waterloo’s Nov. 29, 2012 news release offers more technical detail,

… The model captures biological details of each neuron, including which neurotransmitters are used, how voltages are generated in the cell, and how they communicate. Spaun uses this network of neurons to process visual images in order to control an arm that draws Spaun’s answers to perceptual, cognitive and motor tasks. …

“This is the first model that begins to get at how our brains can perform a wide variety of tasks in a flexible manner—how the brain coordinates the flow of information between different areas to exhibit complex behaviour,” said Professor Chris Eliasmith, Director of the Centre for Theoretical Neuroscience at Waterloo. He is Canada Research Chair in Theoretical Neuroscience, and professor in Waterloo’s Department of Philosophy and Department of Systems Design Engineering.

Unlike other large brain models, Spaun can perform several tasks. Researchers can show patterns of digits and letters the model’s eye, which it then processes, causing it to write its responses to any of eight tasks.  And, just like the human brain, it can shift from task to task, recognizing an object one moment and memorizing a list of numbers the next. [emphasis mine] Because of its biological underpinnings, Spaun can also be used to understand how changes to the brain affect changes to behaviour.

“In related work, we have shown how the loss of neurons with aging leads to decreased performance on cognitive tests,” said Eliasmith. “More generally, we can test our hypotheses about how the brain works, resulting in a better understanding of the effects of drugs or damage to the brain.”

In addition, the model provides new insights into the sorts of algorithms that might be useful for improving machine intelligence. [emphasis mine] For instance, it suggests new methods for controlling the flow of information through a large system attempting to solve challenging cognitive tasks.

Laura Sanders’ Nov. 29, 2012 article for ScienceNews suggests that there is some controversy as to whether or not SPAUN does resemble a human brain,

… Henry Markram, who leads a different project to reconstruct the human brain called the Blue Brain, questions whether Spaun really captures human brain behavior. Because Spaun’s design ignores some important neural properties, it’s unlikely to reveal anything about the brain’s mechanics, says Markram, of the Swiss Federal Institute of Technology in Lausanne. “It is not a brain model.”

Personally, I have a little difficulty seeing lines of code as ever being able to truly simulate brain activity. I think the notion of moving to something simpler (using fewer neurons as the Eliasmith team does) is a move in the right direction but I’m still more interested in devices such as the memristor and the electrochemical atomic switch and their potential.

Blue Brain Project

Memristor and artificial synapses in my April 19, 2012 posting

Atomic or electrochemical atomic switches and neuromorphic engineering briefly mentioned (scroll 1/2 way down) in my Oct. 17, 2011 posting.

ETA Dec. 19, 2012: There was an AMA (ask me anything) session on Reddit with the SPAUN team in early December, if you’re interested, you can still access the questions and answers,

We are the computational neuroscientists behind the world’s largest functional brain model

Medusa, jellyfish, and tissue engineering

The ‘Medusoid’ is a reverse- tissue-engineered jellyfish designed by a collaborative team of researchers based, respectively, at the California Institute of Technology (Caltech) and Harvard University. From the July 22, 2012 news item on ScienceDaily,

When one observes a colorful jellyfish pulsating through the ocean, Greek mythology probably doesn’t immediately come to mind. But the animal once was known as the medusa, after the snake-haired mythological creature its tentacles resemble. The mythological Medusa’s gaze turned people into stone, and now, thanks to recent advances in bio-inspired engineering, a team led by researchers at the California Institute of Technology (Caltech) and Harvard University have flipped that fable on its head: turning a solid element—silicon—and muscle cells into a freely swimming “jellyfish.”

“A big goal of our study was to advance tissue engineering,” says Janna Nawroth, a doctoral student in biology at Caltech and lead author of the study. “In many ways, it is still a very qualitative art [emphasis mine], with people trying to copy a tissue or organ just based on what they think is important or what they see as the major components—without necessarily understanding if those components are relevant to the desired function or without analyzing first how different materials could be used.” Because a particular function—swimming, say—doesn’t necessarily emerge just from copying every single element of a swimming organism into a design, “our idea,” she says, “was that we would make jellyfish functions—swimming and creating feeding currents—as our target and then build a structure based on that information.”

Oops! I’m not sure why Nawroth uses the word ‘qualitative’ here. It’s certainly inappropriate given my understanding of the word. Here’s my rough definition, if anyone has anything better or can explain why Nawroth used ‘qualitative’  in that context, please do comment. I’m going to start by contrasting qualitative with quantitative, both of which I’m going to hugely oversimplify. Quantitative data offers numbers, e.g. 50,000 people committed suicide last year. Qualitative data helps offer insight into why. Researchers can obtain the quantitative data from police records, vital statistics, surveys, etc. where qualitative data is gathered from ‘story-oriented’ or highly detailed personal interviews. ( I would have used ‘hit or miss,’ ‘guesswork,’ or simply used the word art without qualifying it  in this context.)

The originating July 22, 2012 news release from Caltech goes on to describe why jellyfish were selected and how the collaboration between Harvard and Caltech came about,

Jellyfish are believed to be the oldest multi-organ animals in the world, possibly existing on Earth for the past 500 million years. Because they use a muscle to pump their way through the water, their function—on a very basic level—is similar to that of a human heart, which makes the animal a good biological system to analyze for use in tissue engineering.

“It occurred to me in 2007 that we might have failed to understand the fundamental laws of muscular pumps,” says Kevin Kit Parker, Tarr Family Professor of Bioengineering and Applied Physics at Harvard and a coauthor of the study. “I started looking at marine organisms that pump to survive. Then I saw a jellyfish at the New England Aquarium, and I immediately noted both similarities and differences between how the jellyfish pumps and the human heart. The similarities help reveal what you need to do to design a bio-inspired pump.”

Parker contacted John Dabiri, professor of aeronautics and bioengineering at Caltech—and Nawroth’s advisor—and a partnership was born. Together, the two groups worked for years to understand the key factors that contribute to jellyfish propulsion, including the arrangement of their muscles, how their bodies contract and recoil, and how fluid-dynamic effects help or hinder their movements. Once these functions were well understood, the researchers began to design the artificial jellyfish.

Here’s how they created the ‘Medusoid’ (artificial jellyfish, from the July 22, 2012 Harvard University news release on EurekAlert,

To reverse engineer a medusa jellyfish, the investigators used analysis tools borrowed from the fields of law enforcement biometrics and crystallography to make maps of the alignment of subcellular protein networks within all of the muscle cells within the animal. They then conducted studies to understand the electrophysiological triggering of jellyfish propulsion and the biomechanics of the propulsive stroke itself.

Based on such understanding, it turned out that a sheet of cultured rat heart muscle tissue that would contract when electrically stimulated in a liquid environment was the perfect raw material to create an ersatz jellyfish. The team then incorporated a silicone polymer that fashions the body of the artificial creature into a thin membrane that resembles a small jellyfish, with eight arm-like appendages.

Using the same analysis tools, the investigators were able to quantitatively match the subcellular, cellular, and supracellular architecture of the jellyfish musculature with the rat heart muscle cells.

The artificial construct was placed in container of ocean-like salt water and shocked into swimming with synchronized muscle contractions that mimic those of real jellyfish. (In fact, the muscle cells started to contract a bit on their own even before the electrical current was applied.)

“I was surprised that with relatively few components—a silicone base and cells that we arranged—we were able to reproduce some pretty complex swimming and feeding behaviors that you see in biological jellyfish,” says Dabiri.

Their design strategy, they say, will be broadly applicable to the reverse engineering of muscular organs in humans.

For future research direction I’ve excerpted this from the Caltech news release,

The team’s next goal is to design a completely self-contained system that is able to sense and actuate on its own using internal signals, as human hearts do. Nawroth and Dabiri would also like for the Medusoid to be able to go out and gather food on its own. Then, researchers could think about systems that could live in the human body for years at a time without having to worry about batteries because the system would be able to fend for itself. For example, these systems could be the basis for a pacemaker made with biological elements.

“We’re reimagining how much we can do in terms of synthetic biology,” says Dabiri. “A lot of work these days is done to engineer molecules, but there is much less effort to engineer organisms. I think this is a good glimpse into the future of re-engineering entire organisms for the purposes of advancing biomedical technology. We may also be able to engineer applications where these biological systems give us the opportunity to do things more efficiently, with less energy usage.”

I think this excerpt from the Harvard news release provides some insight into at least some of the motivations behind this work,

In addition to advancing the field of tissue engineering, Parker adds that he took on the challenge of building a creature to challenge the traditional view of synthetic biology which is “focused on genetic manipulations of cells.” Instead of building just a cell, he sought to “build a beast.”

A little competitive, eh?

For anyone who’s interested in reading the research (which is behind a paywall), from the ScienceDaily news item,

Janna C Nawroth, Hyungsuk Lee, Adam W Feinberg, Crystal M Ripplinger, Megan L McCain, Anna Grosberg, John O Dabiri & Kevin Kit Parker. A tissue-engineered jellyfish with biomimetic propulsion. Nature Biotechnology, 22 July 2012 DOI: 10.1038/nbt.2269

Andrew Maynard weighs in on the matter with his July 22, 2012 posting titled, We took a rat apart and rebuilt it as a jellyfish, on the 2020Science blog (Note: I have removed links),

 Sometimes you read a science article and it sends a tingle down your spine. That was my reaction this afternoon reading Ed Yong’s piece on a paper just published in Nature Biotechnology by Janna Nawroth, Kevin Kit Parker and colleagues.

The gist of the work is that Parker’s team have created a hybrid biological machine that “swims” like a jellyfish by growing rat heart muscle cells on a patterned sheet of polydimethylsiloxane.  The researchers are using the technique to explore muscular pumps, but the result opens the door to new technologies built around biological-non biological hybrids.

Ed Yong’s July 22, 2012 article for Nature (as mentioned by Andrew) offers a wider perspective on the work than is immediately evident in either of the news releases (Note: I have removed a footnote),

Bioengineers have made an artificial jellyfish using silicone and muscle cells from a rat’s heart. The synthetic creature, dubbed a medusoid, looks like a flower with eight petals. When placed in an electric field, it pulses and swims exactly like its living counterpart.

“Morphologically, we’ve built a jellyfish. Functionally, we’ve built a jellyfish. Genetically, this thing is a rat,” says Kit Parker, a biophysicist at Harvard University in Cambridge, Massachusetts, who led the work. The project is described today in Nature Biotechnology.

….

“I think that this is terrific,” says Joseph Vacanti, a tissue engineer at Massachusetts General Hospital in Boston. “It is a powerful demonstration of engineering chimaeric systems of living and non-living components.”

Here’s a video from the researchers demonstrating the artificial jellyfish in action,

There’s a lot of material for contemplation but what I’m going to note here is the difference in the messaging. The news releases from the ‘universities’ are very focused on the medical application where the discussion in the science community revolves primarily around the synthetic biology/bioengineering elements. It seems to me that this strategy can lead to future problems with a population that is largely unprepared to deal with the notion of mixing and recombining  genetic material or demonstrations of “of engineering chimaeric systems of living and non-living components.”

Advertising for the 21st Century: B-Reel, ‘storytelling’, and mind control

Erin Schulte at Fast Company introduced me to B-Reel, a digital production company, via her Sept. 30, 2011 posting,

Though Swedish hybrid production company B-Reel has been around since 1999, merging film, interactive, games, and mobile to create new methods of storytelling, it exploded into the broader consciousness with 2010’s “The Wilderness Downtown.”

The interactive short film dreamed up by Chris Milk and the band Arcade Fire for its song “We Used To Wait” is a Gen-Y paean of childhood nostalgia, where the singer pines for a simpler, not-so-far away yesteryear where people wrote love letters on paper and anxiously awaited the arrival of an envelope in return.

Here’s a description (followed by B-Reel’s promotiional video) of the Wilderness Downtown project, which was initiated by Google, from the company website,

Featuring Arcade Fire’s new single “We Used To Wait” from their latest album The Suburbs, The Wilderness Downtown is an interactive music video built in HTML 5, using Google Maps and Street-view for Google Chrome Experiments. The film takes an intimate approach by prompting users to input an address from their childhood which then places them at the center of the film’s narrative. Viewers see themselves in the film as they run through the streets of their old neighborhood and finally reach their childhood home. This is tied very closely to the song’s lyrics to make for a powerful emotional experience.

Here’s the video,

The making of the Wilderness Downtown. from B-Reel & B-Reel Films on Vimeo.

A subtle form of advertising for Google, this showcases some of the more innovative approaches that B-Reel takes to its work.

I did watch the Fast Company video interview with Anders Wahlquist, B-Reel Chief Executive Officer, which is included with Schulte’s posting, and he mentions that he founded the company with the intention of combining filmmaking, storytelling, and interactivity. It’s interesting how often the words storytelling and story are used  in the service of advertising and marketing but to replace those words, i.e., it’s no longer about advertising; it’s about telling your story or possibly it’s about mind control. From the July 21, 2011 posting on the B-Reel website,

From B-Reel’s secret laboratory comes a brain-bending experimental project utilising a number of cutting edge tech tools. B-Reel’s UK creative director Riccardo Giraldi led the development of the project, and you can view the explanatory video here, as well as some of the creative musings in a write up below.

The idea is quite simple.

What if you could run a slot car race using your brain?

We did a bit of research on this and it didn’t take long to realise we already have all we need to make these ideas come to life; we just needed to connect the dots and find an easier way to integrate different disciplines to make the magic happen.

These are the steps B-Reel went through:

– researched components and library we could have used

– procured a device that reads mind signals, a Scalextric, Arduino, some tools and electric components

– designed a small electronic circuit to connect Arduino to Scalextric

– wrote the Arduino script to control the Scalextric

– wrote a small Processing application to control the car with the computer mouse

– connected the brain reader device signal to the Scalextric

There are few commercial devices that claim to safely read your brain signals. We ended up choosing the Mindwave headset from Neurosky for this experiment because of its unobtrusive design and its affordable price.

Then we got a basic version Scalextric and started to play around with it. Slot cars are awesome. Digital is already the past – tangible is the future. The principle is straightforward: there are two cars on separate tracks that you can control with a handset. The more current you let pass through the handset, the faster the cars go.

Here’s the ‘mind control’ video,

B-Reel Performs Mind Tricks from B-Reel & B-Reel Films on Vimeo.

I wrote about rats with robotic brains and monkeys (at Duke University in the US) that control robots  in Japan with their thoughts in my Oct. 4, 2011 posting.  I find the resemblance between these projects disconcertingly close and I have to admit I would not have considered advertising applications at this stage of the technology development.

If you are interested in more about mind control projects, Ed Yong at his Not Exactly Rocket Science blog (on the Discover blog network) has written an Oct. 5, 2011 posting titled, Monkeys grab and feel virtual objects with thoughs alone (and what this means for the World Cup). Excerpted from the posting,

This is where we are now: at Duke University, a monkey controls a virtual arm using only its thoughts. Miguel Nicolelis had fitted the animal with a headset of electrodes that translates its brain activity into movements. It can grab virtual objects without using its arms. It can also feel the objects without its hands, because the headset stimulates its brain to create the sense of different textures. Monkey think, monkey do, monkey feel – all without moving a muscle.
And this is where  Nicolelis wants to be in three years: a young quadriplegic Brazilian man strolls confidently into a massive stadium. He controls his four prosthetic limbs with his thoughts, and they in turn send tactile information straight to his brain. The technology melds so fluidly with his mind that he confidently runs up and delivers the opening kick of the 2014 World Cup.

This sounds like a far-fetched dream, but Nicolelis – a big soccer fan – is talking to the Brazilian government to make it a reality. He has created an international consortium called the Walk Again Project, consisting of non-profit research institutions in the United States, Brazil, Germany and Switzerland. Their goal is to create a “high performance brain-controlled prosthetic device that enables patients to finally leave the wheelchair behind.”

I’m not sure what the* intention was in 1999 when the company name, B-Reel, was chosen but today the wordplay has a haunting quality. Especially when you consider that mind control doesn’t necessarily mean people are in control. After all there’s my Sept. 28, 2011 posting about full size vehicles titled Cars that read minds? If you notice, the researcher at B-Reel has to shift his brain function in order to exert control so who’s in charge the researcher or the model car? Extending that question, will you have to change your mind so the car can read it?

* ‘the’ added May 15, 2014.

Science education for children in Europe, so what’s happening in BC?

I’ve been informally collecting information about children’s science education for a few months when yesterday there was a sudden explosion of articles (well, there were three) on the subject.

First off, a science game was launched by the European Commission titled Power of Research. From the March 2, 2011 news item on Nanowerk,

A new strategy browser game – the “Power of research” – is officially launched. Supported by the European Commission, “Power of Research” has been developed to inspire young Europeans to pursue scientific careers and disseminate interesting up-to-date scientific information. Players assume the role of scientists working in a virtual research environment that replicates the situations that scientists have to deal with in the real world. The game, which can be played for free under www.powerofresearch.eu, is expected to create a large community of more than 100,000 players who will be able to communicate in real time via a state of the art interface.

They really do mean it when they say they’re replicating real life situations but the focus is on medical science research and I don’t think the game title makes that clear. Yes, there are many similarities between the situations that scientists of any stripe encounter in their labs but there are also some significant differences between them. In any event,

In “Power of Research” players can engage in “virtual” health research projects, by performing microscopy, protein isolation and DNA experiments, publishing research results, participating in conferences, managing high tech equipment and staff or request funding – all tasks of real researchers. The decisive game elements are communication, collaboration and competition: players can compete against each other in real time or collaborate to become a successful virtual researcher, win scientific awards or become the leader of a research institute.

The game connects the players to the real world. It is based on up-to-date science content and players work on real world research topics inspired by the FP7 health research programme that will be regularly updated. Popular science events, real research institutes, universities and European health research projects form part of the game. Players also have access to a knowledge platform, where they can search in a virtual library, zoom-into real scientific images and learn more about Nobel Prize laureates. European science institutions and hospitals will have the possibility to contribute to the game and provide details about their research.

I like the immersiveness and the game aspect of this project very much. I do wish they were a little more clear about exactly what kind of research the player will engage in. From the Power of Research About webpage,

Your researcher

* Become a famous researcher in “Power of Research”

* Research different topics through exciting research projects

* Play together with your friends and other players from all over the world

* Earn reputation, win science prizes and more …

* Gain special skills and knowledge in 9 different main research areas (like Brain, Paediatrics, …)

* Become a leader in your institute and lead it to international ranks

* The game is 100% free and needs no prior knowledge

Meanwhile, there are more projects. From the March 2, 2011 news item on physorg.com,

Children who are taught how to think and act like scientists develop a clearer understanding of the subject, a study has shown.

The research project led by The University of Nottingham and The Open University has shown that school children who took the lead in investigating science topics of interest to them gained an understanding of good scientific practice.

The study shows that this method of ‘personal inquiry’ could be used to help children develop the skills needed to weigh up misinformation in the media, understand the impact of science and technology on everyday life and help them to make better personal decisions on issues including diet, health and their own effect on the environment.

The three-year project involved providing pupils aged 11 to 14 at Hadden Park High School in Bilborough, Nottingham, and Oakgrove School in Milton Keynes with a new computer toolkit named nQuire, now available as a free download for teachers and schools.

The pupils were given wide themes for their studies but were asked to decide on more specific topics that were of interest to them, including heart rate and fitness, micro climates, healthy eating, sustainability and the effect of noise pollution on birds.

The flexible nature of the toolkit meant that children could become “science investigators”, starting an inquiry in the classroom then collecting data in the playground, at a local nature reserve, or even at home, then sharing and analysing their findings back in class.

Immersive and engaging, yes? I have gone to the nQuire website and while I haven’t downloaded the software, I did successfully log in to the demonstration, in other words, the demonstration is not limited to a UK-based audience.

Meanwhile there’s this project but it seems to be different. It’s spelled differently, INQUIRE, and the focus is on the teachers. From a March 2, 2011 news item on Science Daily,

Thousands of schoolchildren will soon be asking the questions when inquiry-based learning comes to science classrooms across Europe, turning the traditional model of science teaching on its head. The pan-European INQUIRE programme is an exciting new teacher-training initiative delivered by a seventeen-strong consortium of botanic gardens, natural history museums, universities and NGOs.

Coordinated by Innsbruck University Botanic Garden, with support from London-based Botanic Gardens Conservation International (BGCI), INQUIRE is a practical, one-year, continual professional development (CPD) course targeted at qualified teachers working in eleven European countries. Its focus on inquiry-based science education (IBSE) reflects a consensus in the science education community that IBSE methods are more effective than current teaching practices.

Designed to reflect how students actually learn, IBSE also engages them in the process of scientific inquiry. Increasingly it is seen as key to developing their scientific literacy, enhancing their understanding of scientific concepts and heightening their appreciation of how science works. Whereas traditional teaching methods have failed to engage many students, especially in developed countries, IBSE offers outstanding opportunities for effective and enjoyable teaching and learning.

Biodiversity loss and global climate change, among the major scientific as well as political challenges of our age, are core INQUIRE concerns.

That final sentence fragment is a  little puzzling but I believe they’re describing their scientific focus.

My favourite of these projects is one I came across in December 2010 when children from a school in England had a research paper about bees published by the Royal Society’s Biology Letters. You still can access the paper (according to another blogger, Ed Yong, open access would only last to the new year in 2011 but they must have changed their minds). The paper is titled Blackawton bees and lists 30 authors.

1. P. S. Blackawton,
2. S. Airzee,
3. A. Allen,
4. S. Baker,
5. A. Berrow,
6. C. Blair,
7. M. Churchill,
8. J. Coles,
9. R. F.-J. Cumming,
10. L. Fraquelli,
11. C. Hackford,
12. A. Hinton Mellor,
13. M. Hutchcroft,
14. B. Ireland,
15. D. Jewsbury,
16. A. Littlejohns,
17. G. M. Littlejohns,
18. M. Lotto,
19. J. McKeown,
20. A. O’Toole,
21. H. Richards,
22. L. Robbins-Davey,
23. S. Roblyn,
24. H. Rodwell-Lynn,
25. D. Schenck,
26. J. Springer,
27. A. Wishy,
28. T. Rodwell-Lynn,
29. D. Strudwick and
30. R. B. Lotto

This is from the introduction to the paper,

(a) Once upon a time …

People think that humans are the smartest of animals, and most people do not think about other animals as being smart, or at least think that they are not as smart as humans. Knowing that other animals are as smart as us means we can appreciate them more, which could also help us to help them.

If you don’t ever read another science paper in your life, read this one. For the back story on this project, here’s Ed Yong on his Not Exactly Rocket Science blog (a Discover blog) in a December 21, 2010 posting,

“We also discovered that science is cool and fun because you get to do stuff that no one has ever done before.”

This is the conclusion of a new paper published in Biology Letters, a high-powered journal from the UK’s prestigious Royal Society. If its tone seems unusual, that’s because its authors are children from Blackawton Primary School in Devon, England. Aged between 8 and 10, the 25 children have just become the youngest scientists to ever be published in a Royal Society journal.

Their paper, based on fieldwork carried out in a local churchyard, describes how bumblebees can learn which flowers to forage from with more flexibility than anyone had thought. It’s the culmination of a project called ‘i, scientist’, designed to get students to actually carry out scientific research themselves. The kids received some support from Beau Lotto, a neuroscientist at UCL [University College London], and David Strudwick, Blackawton’s head teacher. But the work is all their own.

Yong’s posting features a video of  the  i, scientist project mentioned in the posting, images, and, of course, the rest of the back story.

As it turns out one of my favourite science education/engagement projects is taking place right now (this is based in the UK), I’m a scientist, Get me out of Here!, from their website home page,

I’m a Scientist, Get me out of Here! is an award-winning science enrichment and engagement activity, funded by the Wellcome Trust. It takes place online over a two week period. It’s an X Factor-style competition for scientists, where students are the judges. Scientists and students talk online on this website. They both break down barriers, have fun and learn. But only the students get to vote.

You can view the scientist/student conversations by picking a zone: Argon, Chlorine, Potassium, Forensic, Space, or Stem Cell. The questions the kids ask are fascinating, anything from What’s your favourite colour? to Do you think humans will evolve more? The conversations that ensue can be quite stimulating. This project has been mentioned here before in my June 15, 2010 posting, April 13, 2010 posting (scroll down) and  March 26, 2010 posting (scroll down).

ETA Mar. 3, 2011: The scientists get quite involved and can go to some lengths to win. Here’s Tom Hartley’s video from last year’s (2010) event,

I find the contrast between these kinds of science education/engagement projects in the UK and in Europe and what seems to be a dearth of these in my home province British Columbia (Canada) to be striking. I’ve commented previously on BC’s Year of Science initiative currently taking place in a Dec. 30, 2010 posting where I was commenting on a lack of science culture in Canada. Again, I applaud the initiative while I would urge that in future a less traditional and top/down approach is taken. The Europeans and the British are making science fun by engaging in imaginative and substantive ways. Imagine what getting a paper published in a prestigious science journal does for you (regardless of your age)!