Tag Archives: Harvard University

Congratulate China on the world’s first quantum communication network

China has some exciting news about the world’s first quantum network; it’s due to open in late August 2017 so you may want to have your congratulations in order for later this month.

An Aug. 4, 2017 news item on phys.org makes the announcement,

As malicious hackers find ever more sophisticated ways to launch attacks, China is about to launch the Jinan Project, the world’s first unhackable computer network, and a major milestone in the development of quantum technology.

Named after the eastern Chinese city where the technology was developed, the network is planned to be fully operational by the end of August 2017. Jinan is the hub of the Beijing-Shanghai quantum network due to its strategic location between the two principal Chinese metropolises.

“We plan to use the network for national defence, finance and other fields, and hope to spread it out as a pilot that if successful can be used across China and the whole world,” commented Zhou Fei, assistant director of the Jinan Institute of Quantum Technology, who was speaking to Britain’s Financial Times.

An Aug. 3, 2017 CORDIS (Community Research and Development Research Information Service [for the European Commission]) press release, which originated the news item, provides more detail about the technology,

By launching the network, China will become the first country worldwide to implement quantum technology for a real life, commercial end. It also highlights that China is a key global player in the rush to develop technologies based on quantum principles, with the EU and the United States also vying for world leadership in the field.

The network, known as a Quantum Key Distribution (QKD) network, is more secure than widely used electronic communication equivalents. Unlike a conventional telephone or internet cable, which can be tapped without the sender or recipient being aware, a QKD network alerts both users to any tampering with the system as soon as it occurs. This is because tampering immediately alters the information being relayed, with the disturbance being instantly recognisable. Once fully implemented, it will make it almost impossible for other governments to listen in on Chinese communications.

In the Jinan network, some 200 users from China’s military, government, finance and electricity sectors will be able to send messages safe in the knowledge that only they are reading them. It will be the world’s longest land-based quantum communications network, stretching over 2 000 km.

Also speaking to the ‘Financial Times’, quantum physicist Tim Byrnes, based at New York University’s (NYU) Shanghai campus commented: ‘China has achieved staggering things with quantum research… It’s amazing how quickly China has gotten on with quantum research projects that would be too expensive to do elsewhere… quantum communication has been taken up by the commercial sector much more in China compared to other countries, which means it is likely to pull ahead of Europe and US in the field of quantum communication.’

However, Europe is also determined to also be at the forefront of the ‘quantum revolution’ which promises to be one of the major defining technological phenomena of the twenty-first century. The EU has invested EUR 550 million into quantum technologies and has provided policy support to researchers through the 2016 Quantum Manifesto.

Moreover, with China’s latest achievement (and a previous one already notched up from July 2017 when its quantum satellite – the world’s first – sent a message to Earth on a quantum communication channel), it looks like the race to be crowned the world’s foremost quantum power is well and truly underway…

Prior to this latest announcement, Chinese scientists had published work about quantum satellite communications, a development that makes their imminent terrestrial quantum network possible. Gabriel Popkin wrote about the quantum satellite in a June 15, 2017 article Science magazine,

Quantum entanglement—physics at its strangest—has moved out of this world and into space. In a study that shows China’s growing mastery of both the quantum world and space science, a team of physicists reports that it sent eerily intertwined quantum particles from a satellite to ground stations separated by 1200 kilometers, smashing the previous world record. The result is a stepping stone to ultrasecure communication networks and, eventually, a space-based quantum internet.

“It’s a huge, major achievement,” says Thomas Jennewein, a physicist at the University of Waterloo in Canada. “They started with this bold idea and managed to do it.”

Entanglement involves putting objects in the peculiar limbo of quantum superposition, in which an object’s quantum properties occupy multiple states at once: like Schrödinger’s cat, dead and alive at the same time. Then those quantum states are shared among multiple objects. Physicists have entangled particles such as electrons and photons, as well as larger objects such as superconducting electric circuits.

Theoretically, even if entangled objects are separated, their precarious quantum states should remain linked until one of them is measured or disturbed. That measurement instantly determines the state of the other object, no matter how far away. The idea is so counterintuitive that Albert Einstein mocked it as “spooky action at a distance.”

Starting in the 1970s, however, physicists began testing the effect over increasing distances. In 2015, the most sophisticated of these tests, which involved measuring entangled electrons 1.3 kilometers apart, showed once again that spooky action is real.

Beyond the fundamental result, such experiments also point to the possibility of hack-proof communications. Long strings of entangled photons, shared between distant locations, can be “quantum keys” that secure communications. Anyone trying to eavesdrop on a quantum-encrypted message would disrupt the shared key, alerting everyone to a compromised channel.

But entangled photons degrade rapidly as they pass through the air or optical fibers. So far, the farthest anyone has sent a quantum key is a few hundred kilometers. “Quantum repeaters” that rebroadcast quantum information could extend a network’s reach, but they aren’t yet mature. Many physicists have dreamed instead of using satellites to send quantum information through the near-vacuum of space. “Once you have satellites distributing your quantum signals throughout the globe, you’ve done it,” says Verónica Fernández Mármol, a physicist at the Spanish National Research Council in Madrid. …

Popkin goes on to detail the process for making the discovery in easily accessible (for the most part) writing and in a video and a graphic.

Russell Brandom writing for The Verge in a June 15, 2017 article about the Chinese quantum satellite adds detail about previous work and teams in other countries also working on the challenge (Note: Links have been removed),

Quantum networking has already shown promise in terrestrial fiber networks, where specialized routing equipment can perform the same trick over conventional fiber-optic cable. The first such network was a DARPA-funded connection established in 2003 between Harvard, Boston University, and a private lab. In the years since, a number of companies have tried to build more ambitious connections. The Swiss company ID Quantique has mapped out a quantum network that would connect many of North America’s largest data centers; in China, a separate team is working on a 2,000-kilometer quantum link between Beijing and Shanghai, which would rely on fiber to span an even greater distance than the satellite link. Still, the nature of fiber places strict limits on how far a single photon can travel.

According to ID Quantique, a reliable satellite link could connect the existing fiber networks into a single globe-spanning quantum network. “This proves the feasibility of quantum communications from space,” ID Quantique CEO Gregoire Ribordy tells The Verge. “The vision is that you have regional quantum key distribution networks over fiber, which can connect to each other through the satellite link.”

China isn’t the only country working on bringing quantum networks to space. A collaboration between the UK’s University of Strathclyde and the National University of Singapore is hoping to produce the same entanglement in cheap, readymade satellites called Cubesats. A Canadian team is also developing a method of producing entangled photons on the ground before sending them into space.

I wonder if there’s going to be an invitational event for scientists around the world to celebrate the launch.

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

Machine learning programs learn bias

The notion of bias in artificial intelligence (AI)/algorithms/robots is gaining prominence (links to other posts featuring algorithms and bias are at the end of this post). The latest research concerns machine learning where an artificial intelligence system trains itself with ordinary human language from the internet. From an April 13, 2017 American Association for the Advancement of Science (AAAS) news release on EurekAlert,

As artificial intelligence systems “learn” language from existing texts, they exhibit the same biases that humans do, a new study reveals. The results not only provide a tool for studying prejudicial attitudes and behavior in humans, but also emphasize how language is intimately intertwined with historical biases and cultural stereotypes. A common way to measure biases in humans is the Implicit Association Test (IAT), where subjects are asked to pair two concepts they find similar, in contrast to two concepts they find different; their response times can vary greatly, indicating how well they associated one word with another (for example, people are more likely to associate “flowers” with “pleasant,” and “insects” with “unpleasant”). Here, Aylin Caliskan and colleagues developed a similar way to measure biases in AI systems that acquire language from human texts; rather than measuring lag time, however, they used the statistical number of associations between words, analyzing roughly 2.2 million words in total. Their results demonstrate that AI systems retain biases seen in humans. For example, studies of human behavior show that the exact same resume is 50% more likely to result in an opportunity for an interview if the candidate’s name is European American rather than African-American. Indeed, the AI system was more likely to associate European American names with “pleasant” stimuli (e.g. “gift,” or “happy”). In terms of gender, the AI system also reflected human biases, where female words (e.g., “woman” and “girl”) were more associated than male words with the arts, compared to mathematics. In a related Perspective, Anthony G. Greenwald discusses these findings and how they could be used to further analyze biases in the real world.

There are more details about the research in this April 13, 2017 Princeton University news release on EurekAlert (also on ScienceDaily),

In debates over the future of artificial intelligence, many experts think of the new systems as coldly logical and objectively rational. But in a new study, researchers have demonstrated how machines can be reflections of us, their creators, in potentially problematic ways. Common machine learning programs, when trained with ordinary human language available online, can acquire cultural biases embedded in the patterns of wording, the researchers found. These biases range from the morally neutral, like a preference for flowers over insects, to the objectionable views of race and gender.

Identifying and addressing possible bias in machine learning will be critically important as we increasingly turn to computers for processing the natural language humans use to communicate, for instance in doing online text searches, image categorization and automated translations.

“Questions about fairness and bias in machine learning are tremendously important for our society,” said researcher Arvind Narayanan, an assistant professor of computer science and an affiliated faculty member at the Center for Information Technology Policy (CITP) at Princeton University, as well as an affiliate scholar at Stanford Law School’s Center for Internet and Society. “We have a situation where these artificial intelligence systems may be perpetuating historical patterns of bias that we might find socially unacceptable and which we might be trying to move away from.”

The paper, “Semantics derived automatically from language corpora contain human-like biases,” published April 14  [2017] in Science. Its lead author is Aylin Caliskan, a postdoctoral research associate and a CITP fellow at Princeton; Joanna Bryson, a reader at University of Bath, and CITP affiliate, is a coauthor.

As a touchstone for documented human biases, the study turned to the Implicit Association Test, used in numerous social psychology studies since its development at the University of Washington in the late 1990s. The test measures response times (in milliseconds) by human subjects asked to pair word concepts displayed on a computer screen. Response times are far shorter, the Implicit Association Test has repeatedly shown, when subjects are asked to pair two concepts they find similar, versus two concepts they find dissimilar.

Take flower types, like “rose” and “daisy,” and insects like “ant” and “moth.” These words can be paired with pleasant concepts, like “caress” and “love,” or unpleasant notions, like “filth” and “ugly.” People more quickly associate the flower words with pleasant concepts, and the insect terms with unpleasant ideas.

The Princeton team devised an experiment with a program where it essentially functioned like a machine learning version of the Implicit Association Test. Called GloVe, and developed by Stanford University researchers, the popular, open-source program is of the sort that a startup machine learning company might use at the heart of its product. The GloVe algorithm can represent the co-occurrence statistics of words in, say, a 10-word window of text. Words that often appear near one another have a stronger association than those words that seldom do.

The Stanford researchers turned GloVe loose on a huge trawl of contents from the World Wide Web, containing 840 billion words. Within this large sample of written human culture, Narayanan and colleagues then examined sets of so-called target words, like “programmer, engineer, scientist” and “nurse, teacher, librarian” alongside two sets of attribute words, such as “man, male” and “woman, female,” looking for evidence of the kinds of biases humans can unwittingly possess.

In the results, innocent, inoffensive biases, like for flowers over bugs, showed up, but so did examples along lines of gender and race. As it turned out, the Princeton machine learning experiment managed to replicate the broad substantiations of bias found in select Implicit Association Test studies over the years that have relied on live, human subjects.

For instance, the machine learning program associated female names more with familial attribute words, like “parents” and “wedding,” than male names. In turn, male names had stronger associations with career attributes, like “professional” and “salary.” Of course, results such as these are often just objective reflections of the true, unequal distributions of occupation types with respect to gender–like how 77 percent of computer programmers are male, according to the U.S. Bureau of Labor Statistics.

Yet this correctly distinguished bias about occupations can end up having pernicious, sexist effects. An example: when foreign languages are naively processed by machine learning programs, leading to gender-stereotyped sentences. The Turkish language uses a gender-neutral, third person pronoun, “o.” Plugged into the well-known, online translation service Google Translate, however, the Turkish sentences “o bir doktor” and “o bir hem?ire” with this gender-neutral pronoun are translated into English as “he is a doctor” and “she is a nurse.”

“This paper reiterates the important point that machine learning methods are not ‘objective’ or ‘unbiased’ just because they rely on mathematics and algorithms,” said Hanna Wallach, a senior researcher at Microsoft Research New York City, who was not involved in the study. “Rather, as long as they are trained using data from society and as long as society exhibits biases, these methods will likely reproduce these biases.”

Another objectionable example harkens back to a well-known 2004 paper by Marianne Bertrand of the University of Chicago Booth School of Business and Sendhil Mullainathan of Harvard University. The economists sent out close to 5,000 identical resumes to 1,300 job advertisements, changing only the applicants’ names to be either traditionally European American or African American. The former group was 50 percent more likely to be offered an interview than the latter. In an apparent corroboration of this bias, the new Princeton study demonstrated that a set of African American names had more unpleasantness associations than a European American set.

Computer programmers might hope to prevent cultural stereotype perpetuation through the development of explicit, mathematics-based instructions for the machine learning programs underlying AI systems. Not unlike how parents and mentors try to instill concepts of fairness and equality in children and students, coders could endeavor to make machines reflect the better angels of human nature.

“The biases that we studied in the paper are easy to overlook when designers are creating systems,” said Narayanan. “The biases and stereotypes in our society reflected in our language are complex and longstanding. Rather than trying to sanitize or eliminate them, we should treat biases as part of the language and establish an explicit way in machine learning of determining what we consider acceptable and unacceptable.”

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

Semantics derived automatically from language corpora contain human-like biases by Aylin Caliskan, Joanna J. Bryson, Arvind Narayanan. Science  14 Apr 2017: Vol. 356, Issue 6334, pp. 183-186 DOI: 10.1126/science.aal4230

This paper appears to be open access.

Links to more cautionary posts about AI,

Aug 5, 2009: Autonomous algorithms; intelligent windows; pretty nano pictures

June 14, 2016:  Accountability for artificial intelligence decision-making

Oct. 25, 2016 Removing gender-based stereotypes from algorithms

March 1, 2017: Algorithms in decision-making: a government inquiry in the UK

There’s also a book which makes some of the current use of AI programmes and big data quite accessible reading: Cathy O’Neil’s ‘Weapons of Math Destruction: How Big Data Increases Inequality and Threatens Democracy’.

Evolution of literature as seen by a classicist, a biologist and a computer scientist

Studying intertextuality shows how books are related in various ways and are reorganized and recombined over time. Image courtesy of Elena Poiata.

I find the image more instructive when I read it from the bottom up. For those who prefer to prefer to read from the top down, there’s this April 5, 2017 University of Texas at Austin news release (also on EurekAlert),

A classicist, biologist and computer scientist all walk into a room — what comes next isn’t the punchline but a new method to analyze relationships among ancient Latin and Greek texts, developed in part by researchers from The University of Texas at Austin.

Their work, referred to as quantitative criticism, is highlighted in a study published in the Proceedings of the National Academy of Sciences. The paper identifies subtle literary patterns in order to map relationships between texts and more broadly to trace the cultural evolution of literature.

“As scholars of the humanities well know, literature is a system within which texts bear a multitude of relationships to one another. Understanding what is distinctive about one text entails knowing how it fits within that system,” said Pramit Chaudhuri, associate professor in the Department of Classics at UT Austin. “Our work seeks to harness the power of quantification and computation to describe those relationships at macro and micro levels not easily achieved by conventional reading alone.”

In the study, the researchers create literary profiles based on stylometric features, such as word usage, punctuation and sentence structure, and use techniques from machine learning to understand these complex datasets. Taking a computational approach enables the discovery of small but important characteristics that distinguish one work from another — a process that could require years using manual counting methods.

“One aspect of the technical novelty of our work lies in the unusual types of literary features studied,” Chaudhuri said. “Much computational text analysis focuses on words, but there are many other important hallmarks of style, such as sound, rhythm and syntax.”

Another component of their work builds on Matthew Jockers’ literary “macroanalysis,” which uses machine learning to identify stylistic signatures of particular genres within a large body of English literature. Implementing related approaches, Chaudhuri and his colleagues have begun to trace the evolution of Latin prose style, providing new, quantitative evidence for the sweeping impact of writers such as Caesar and Livy on the subsequent development of Roman prose literature.

“There is a growing appreciation that culture evolves and that language can be studied as a cultural artifact, but there has been less research focused specifically on the cultural evolution of literature,” said the study’s lead author Joseph Dexter, a Ph.D. candidate in systems biology at Harvard University. “Working in the area of classics offers two advantages: the literary tradition is a long and influential one well served by digital resources, and classical scholarship maintains a strong interest in close linguistic study of literature.”

Unusually for a publication in a science journal, the paper contains several examples of the types of more speculative literary reading enabled by the quantitative methods introduced. The authors discuss the poetic use of rhyming sounds for emphasis and of particular vocabulary to evoke mood, among other literary features.

“Computation has long been employed for attribution and dating of literary works, problems that are unambiguous in scope and invite binary or numerical answers,” Dexter said. “The recent explosion of interest in the digital humanities, however, has led to the key insight that similar computational methods can be repurposed to address questions of literary significance and style, which are often more ambiguous and open ended. For our group, this humanist work of criticism is just as important as quantitative methods and data.”

The paper is the work of the Quantitative Criticism Lab (www.qcrit.org), co-directed by Chaudhuri and Dexter in collaboration with researchers from several other institutions. It is funded in part by a 2016 National Endowment for the Humanities grant and the Andrew W. Mellon Foundation New Directions Fellowship, awarded in 2016 to Chaudhuri to further his education in statistics and biology. Chaudhuri was one of 12 scholars selected for the award, which provides humanities researchers the opportunity to train outside of their own area of special interest with a larger goal of bridging the humanities and social sciences.

Here’s another link to the paper along with a citation,

Quantitative criticism of literary relationships by Joseph P. Dexter, Theodore Katz, Nilesh Tripuraneni, Tathagata Dasgupta, Ajay Kannan, James A. Brofos, Jorge A. Bonilla Lopez, Lea A. Schroeder, Adriana Casarez, Maxim Rabinovich, Ayelet Haimson Lushkov, and Pramit Chaudhuri. PNAS Published online before print April 3, 2017, doi: 10.1073/pnas.1611910114

This paper appears to be open access.

Formation of a time (temporal) crystal

It’s a crystal arranged in time according to a March 8, 2017 University of Texas at Austin news release (also on EurekAlert), Note: Links have been removed,

Salt, snowflakes and diamonds are all crystals, meaning their atoms are arranged in 3-D patterns that repeat. Today scientists are reporting in the journal Nature on the creation of a phase of matter, dubbed a time crystal, in which atoms move in a pattern that repeats in time rather than in space.

The atoms in a time crystal never settle down into what’s known as thermal equilibrium, a state in which they all have the same amount of heat. It’s one of the first examples of a broad new class of matter, called nonequilibrium phases, that have been predicted but until now have remained out of reach. Like explorers stepping onto an uncharted continent, physicists are eager to explore this exotic new realm.

“This opens the door to a whole new world of nonequilibrium phases,” says Andrew Potter, an assistant professor of physics at The University of Texas at Austin. “We’ve taken these theoretical ideas that we’ve been poking around for the last couple of years and actually built it in the laboratory. Hopefully, this is just the first example of these, with many more to come.”

Some of these nonequilibrium phases of matter may prove useful for storing or transferring information in quantum computers.

Potter is part of the team led by researchers at the University of Maryland who successfully created the first time crystal from ions, or electrically charged atoms, of the element ytterbium. By applying just the right electrical field, the researchers levitated 10 of these ions above a surface like a magician’s assistant. Next, they whacked the atoms with a laser pulse, causing them to flip head over heels. Then they hit them again and again in a regular rhythm. That set up a pattern of flips that repeated in time.

Crucially, Potter noted, the pattern of atom flips repeated only half as fast as the laser pulses. This would be like pounding on a bunch of piano keys twice a second and notes coming out only once a second. This weird quantum behavior was a signature that he and his colleagues predicted, and helped confirm that the result was indeed a time crystal.

The team also consists of researchers at the National Institute of Standards and Technology, the University of California, Berkeley and Harvard University, in addition to the University of Maryland and UT Austin.

Frank Wilczek, a Nobel Prize-winning physicist at the Massachusetts Institute of Technology, was teaching a class about crystals in 2012 when he wondered whether a phase of matter could be created such that its atoms move in a pattern that repeats in time, rather than just in space.

Potter and his colleague Norman Yao at UC Berkeley created a recipe for building such a time crystal and developed ways to confirm that, once you had built such a crystal, it was in fact the real deal. That theoretical work was announced publically last August and then published in January in the journal Physical Review Letters.

A team led by Chris Monroe of the University of Maryland in College Park built a time crystal, and Potter and Yao helped confirm that it indeed had the properties they predicted. The team announced that breakthrough—constructing a working time crystal—last September and is publishing the full, peer-reviewed description today in Nature.

A team led by Mikhail Lukin at Harvard University created a second time crystal a month after the first team, in that case, from a diamond.

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

Observation of a discrete time crystal by J. Zhang, P. W. Hess, A. Kyprianidis, P. Becker, A. Lee, J. Smith, G. Pagano, I.-D. Potirniche, A. C. Potter, A. Vishwanath, N. Y. Yao, & C. Monroe. Nature 543, 217–220 (09 March 2017) doi:10.1038/nature21413 Published online 08 March 2017

This paper is behind a paywall.

3D picture language for mathematics

There’s a new, 3D picture language for mathematics called ‘quon’ according to a March 3, 2017 news item on phys.org,

Galileo called mathematics the “language with which God wrote the universe.” He described a picture-language, and now that language has a new dimension.

The Harvard trio of Arthur Jaffe, the Landon T. Clay Professor of Mathematics and Theoretical Science, postdoctoral fellow Zhengwei Liu, and researcher Alex Wozniakowski has developed a 3-D picture-language for mathematics with potential as a tool across a range of topics, from pure math to physics.

Though not the first pictorial language of mathematics, the new one, called quon, holds promise for being able to transmit not only complex concepts, but also vast amounts of detail in relatively simple images. …

A March 2, 2017 Harvard University news release by Peter Reuell, which originated the news item, provides more context for the research,

“It’s a big deal,” said Jacob Biamonte of the Quantum Complexity Science Initiative after reading the research. “The paper will set a new foundation for a vast topic.”

“This paper is the result of work we’ve been doing for the past year and a half, and we regard this as the start of something new and exciting,” Jaffe said. “It seems to be the tip of an iceberg. We invented our language to solve a problem in quantum information, but we have already found that this language led us to the discovery of new mathematical results in other areas of mathematics. We expect that it will also have interesting applications in physics.”

When it comes to the “language” of mathematics, humans start with the basics — by learning their numbers. As we get older, however, things become more complex.

“We learn to use algebra, and we use letters to represent variables or other values that might be altered,” Liu said. “Now, when we look at research work, we see fewer numbers and more letters and formulas. One of our aims is to replace ‘symbol proof’ by ‘picture proof.’”

The new language relies on images to convey the same information that is found in traditional algebraic equations — and in some cases, even more.

“An image can contain information that is very hard to describe algebraically,” Liu said. “It is very easy to transmit meaning through an image, and easy for people to understand what they see in an image, so we visualize these concepts and instead of words or letters can communicate via pictures.”

“So this pictorial language for mathematics can give you insights and a way of thinking that you don’t see in the usual, algebraic way of approaching mathematics,” Jaffe said. “For centuries there has been a great deal of interaction between mathematics and physics because people were thinking about the same things, but from different points of view. When we put the two subjects together, we found many new insights, and this new language can take that into another dimension.”

In their most recent work, the researchers moved their language into a more literal realm, creating 3-D images that, when manipulated, can trigger mathematical insights.

“Where before we had been working in two dimensions, we now see that it’s valuable to have a language that’s Lego-like, and in three dimensions,” Jaffe said. “By pushing these pictures around, or working with them like an object you can deform, the images can have different mathematical meanings, and in that way we can create equations.”

Among their pictorial feats, Jaffe said, are the complex equations used to describe quantum teleportation. The researchers have pictures for the Pauli matrices, which are fundamental components of quantum information protocols. This shows that the standard protocols are topological, and also leads to discovery of new protocols.

“It turns out one picture is worth 1,000 symbols,” Jaffe said.

“We could describe this algebraically, and it might require an entire page of equations,” Liu added. “But we can do that in one picture, so it can capture a lot of information.”

Having found a fit with quantum information, the researchers are now exploring how their language might also be useful in a number of other subjects in mathematics and physics.

“We don’t want to make claims at this point,” Jaffe said, “but we believe and are thinking about quite a few other areas where this picture-language could be important.”

Sadly, there are no artistic images illustrating quon but this is from the paper,

An n-quon is represented by n hemispheres. We call the flat disc on the boundary of each hemisphere a boundary disc. Each hemisphere contains a neutral diagram with four boundary points on its boundary disk. The dotted box designates the internal structure that specifies the quon vector. For example, the 3-quon is represented as

Courtesy: PNAS and Harvard University

I gather the term ‘quon’ is meant to suggest quantum particles.

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

Quon 3D language for quantum information by Zhengwei Liu, Alex Wozniakowski, and Arthur M. Jaffe. Proceedins of the National Academy of Sciences Published online before print February 6, 2017, doi: 10.1073/pnas.1621345114 PNAS March 7, 2017 vol. 114 no. 10

This paper appears to be open access.

Portable nanofibre fabrication device (point-of-use manufacturing)

A portable nanofiber fabrication device is quite an achievement although it seems it’s not quite ready for prime time yet. From a March 1, 2017 news item on Nanowerk (Note: A link has been removed),

Harvard researchers have developed a lightweight, portable nanofiber fabrication device that could one day be used to dress wounds on a battlefield or dress shoppers in customizable fabrics. The research was published recently in Macromolecular Materials and Engineering (“Design and Fabrication of Fibrous Nanomaterials Using Pull Spinning”)

A schematic of the pull spinning apparatus with a side view illustration of a fiber being pulled from the polymer reservoir. The pull spinning system consists of a rotating bristle that dips and pulls a polymer jet in a spiral trajectory (Leila Deravi/Harvard University)

A March 1, 2017 Harvard University news release (also on EurekAlert) by Leah Burrow,, which originated the news item, describes the current process for nanofiber fabrication and explains how this technique is an improvement,

There are many ways to make nanofibers. These versatile materials — whose target applications include everything from tissue engineering to bullet proof vests — have been made using centrifugal force, capillary force, electric field, stretching, blowing, melting, and evaporation.

Each of these fabrication methods has pros and cons. For example, Rotary Jet-Spinning (RJS) and Immersion Rotary Jet-Spinning (iRJS) are novel manufacturing techniques developed in the Disease Biophysics Group at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Wyss Institute for Biologically Inspired Engineering. Both RJS and iRJS dissolve polymers and proteins in a liquid solution and use centrifugal force or precipitation to elongate and solidify polymer jets into nanoscale fibers. These methods are great for producing large amounts of a range of materials – including DNA, nylon, and even Kevlar – but until now they haven’t been particularly portable.

The Disease Biophysics Group recently announced the development of a hand-held device that can quickly produce nanofibers with precise control over fiber orientation. Regulating fiber alignment and deposition is crucial when building nanofiber scaffolds that mimic highly aligned tissue in the body or designing point-of-use garments that fit a specific shape.

“Our main goal for this research was to make a portable machine that you could use to achieve controllable deposition of nanofibers,” said Nina Sinatra, a graduate student in the Disease Biophysics Group and co-first author of the paper. “In order to develop this kind of point-and-shoot device, we needed a technique that could produce highly aligned fibers with a reasonably high throughput.”

The new fabrication method, called pull spinning, uses a high-speed rotating bristle that dips into a polymer or protein reservoir and pulls a droplet from solution into a jet. The fiber travels in a spiral trajectory and solidifies before detaching from the bristle and moving toward a collector. Unlike other processes, which involve multiple manufacturing variables, pull spinning requires only one processing parameter — solution viscosity — to regulate nanofiber diameter. Minimal process parameters translate to ease of use and flexibility at the bench and, one day, in the field.

Pull spinning works with a range of different polymers and proteins. The researchers demonstrated proof-of-concept applications using polycaprolactone and gelatin fibers to direct muscle tissue growth and function on bioscaffolds, and nylon and polyurethane fibers for point-of-wear apparel.

“This simple, proof-of-concept study demonstrates the utility of this system for point-of-use manufacturing,” said Kit Parker, the Tarr Family Professor of Bioengineering and Applied Physics and director of the Disease Biophysics Group. “Future applications for directed production of customizable nanotextiles could extend to spray-on sportswear that gradually heats or cools an athlete’s body, sterile bandages deposited directly onto a wound, and fabrics with locally varying mechanical properties.”

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

Design and Fabrication of Fibrous Nanomaterials Using Pull Spinning by Leila F. Deravi, Nina R. Sinatra, Christophe O. Chantre, Alexander P. Nesmith, Hongyan Yuan, Sahm K. Deravi, Josue A. Goss, Luke A. MacQueen, Mohammad R. Badrossamy, Grant M. Gonzalez, Michael D. Phillips, and Kevin Kit Parker. Macromolecular Materials and Engineering DOI: 10.1002/mame.201600404 Version of Record online: 17 JAN 2017

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

CRISPR patent decision: Harvard’s and MIT’s Broad Institute victorious—for now

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.

But the fight for patent rights to CRISPR technology is by no means over. Here are four reasons why.

1. Berkeley can appeal the ruling

2. European patents are still up for grabs

3. Other parties are also claiming patent rights on CRISPR–Cas9

4. CRISPR technology is moving beyond what the patents cover

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.

Once you’ve read Distor’s and Ledford’s articles, you may want to check out Adam Rogers’ and Eric Niiler’s Feb. 16, 2017 CRISPR patent article for Wired,

The fight over who owns the most promising technique for editing genes—cutting and pasting the stuff of life to cure disease and advance scientific knowledge—has been a rough one. A team on the West Coast, at UC Berkeley, filed patents on the method, Crispr-Cas9; a team on the East Coast, based at MIT and the Broad Institute, filed their own patents in 2014 after Berkeley’s, but got them granted first. The Berkeley group contended that this constituted “interference,” and that Berkeley deserved the patent.

At stake: millions, maybe billions of dollars in biotech money and licensing fees, the future of medicine, the future of bioscience. Not nothing. Who will benefit depends on who owns the patents.

On Wednesday [Feb. 15, 2017], the US Patent Trial and Appeal Board kind of, sort of, almost began to answer that question. Berkeley will get the patent for using the system called Crispr-Cas9 in any living cell, from bacteria to blue whales. Broad/MIT gets the patent in eukaryotic cells, which is to say, plants and animals.

It’s … confusing. “The patent that the Broad received is for the use of Crispr gene-editing technology in eukaryotic cells. The patent for the University of California is for all cells,” says Jennifer Doudna, the UC geneticist and co-founder of Caribou Biosciences who co-invented Crispr, on a conference call. Her metaphor: “They have a patent on green tennis balls; we have a patent for all tennis balls.”

Observers didn’t quite buy that topspin. If Caribou is playing tennis, it’s looking like Broad/MIT is Serena Williams.

“UC does not necessarily lose everything, but they’re no doubt spinning the story,” says Robert Cook-Deegan, an expert in genetic policy at Arizona State University’s School for the Future of Innovation in Society. “UC’s claims to eukaryotic uses of Crispr-Cas9 will not be granted in the form they sought. That’s a big deal, and UC was the big loser.”

UC officials said Wednesday [Feb. 15, 2017] that they are studying the 51-page decision and considering whether to appeal. That leaves members of the biotechnology sector wondering who they will have to pay to use Crispr as part of a business—and scientists hoping the outcome won’t somehow keep them from continuing their research.

….

Happy reading!