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‘Fingerprinting’ and neural nets could help protect power grid, other industrial systems

Electrical substation (credit: Fitrah Hamid, Georgia Tech)

Georgia Tech researchers have developed a device fingerprinting technique that could improve the security of the electrical grid and other industrial systems.

“The stakes are extremely high; the systems are very different from home or office computer networks,” said Raheem Beyah, an associate professor in the School of Electrical and Computer Engineering at the Georgia Institute of Technology.

The networked systems controlling the U.S. electrical grid and other industrial systems, carried out over supervisory control and data acquisition (SCADA) protocols, often lack the ability to run modern encryption and authentication systems. The legacy systems connected to them were never designed for networked security, Beyah said. Because they are distributed around the country, often in remote areas, the systems are also difficult to update using the “patching” techniques common in computer networks.

Fingerprinting to detect false data or commands

Points of attack in a power substation network (credit: David Formby et al./Network and Distributed System Security Symposium)

Which is why Beyah and his team have developed “fingerprinting techniques” to protect various operations of the power grid to prevent or minimize spoofing of packets that could be injected to produce false data or false control commands into the system. “This is the first technique that can passively fingerprint different devices that are part of critical infrastructure networks,” he said. “We believe it can be used to significantly improve the security of the grid and other networks.”

For instance, control devices used in the power grid produce signals that are distinctive because of their unique physical configurations and compositions. Security devices listening to signals traversing the grid’s control systems can differentiate between these legitimate devices and signals produced by equipment that’s not part of the system.

Devices such as circuit breakers and electrical protection systems can also be told to open or close remotely, and they then report on the actions they’ve taken. The time required to open a breaker or a valve is determined by the physical properties of the device. If an acknowledgement arrives too soon after the command is issued — less time than it would take for a breaker or valve to open, for instance — the security system could suspect spoofing, Beyah explained.

To develop the device fingerprints, the researchers have built computer models of utility grid devices to understand how they operate. Information to build the models came from “black box” techniques — watching the information that goes into and out of the system — and “white box” techniques using schematics or physical access to the systems and unique signatures that indicates the identity of specific devices, or device type, or associated actions.

The researchers used supervised learning techniques when a list of IP addresses and corresponding device types were available; and unsupervised learning when not available, with performance nearly as high as the supervised learning methods.

The researchers have demonstrated the technique on two electrical substations, and plan to continue refining it until it becomes close to 100 percent accurate. Their current technique addresses the protocol used for more than half of the devices on the electrical grid, and future work will include examining application of the method to other protocols.

Other vulnerable systems

Beyah believes the approach could have broad application to securing industrial control systems used in manufacturing, oil and gas refining, wastewater treatment and other industries where they use devices with measurable physical properties. Beyond industrial controls, the principle could also apply to the Internet of Things (IoT), where the devices being controlled have specific signatures related to switching them on and off.

“All of these IoT devices will be doing physical things, such as turning your air-conditioning on or off,” Beyah said. “There will be a physical action occurring, which is similar to what we have studied with valves and actuators.”

The research, reported February 23 at the Network and Distributed System Security Symposium in San Diego, was supported in part by the National Science Foundation (NSF). The approach has been successfully tested in two electrical substations.

Abstract of Who’s in Control of Your Control System? Device Fingerprinting for Cyber-Physical Systems

Industrial control system (ICS) networks used in critical infrastructures such as the power grid present a unique set of security challenges. The distributed networks are difficult to physically secure, legacy equipment can make cryptography and regular patches virtually impossible, and compromises can result in catastrophic physical damage. To address these concerns, this research proposes two device type fingerprinting methods designed to augment existing intrusion detection methods in the ICS environment. The first method measures data response processing times and takes advantage of the static and low-latency nature of dedicated ICS networks to develop accurate fingerprints, while the second method uses the physical operation times to develop a unique signature for each device type. Additionally, the physical fingerprinting method is extended to develop a completely new class of fingerprint generation that requires neither prior access to the network nor an example target device. Fingerprint classification accuracy is evaluated using a combination of a real world five month dataset from a live power substation and controlled lab experiments. Finally, simple forgery attempts are launched against the methods to investigate their strength under attack.

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Engineered swarmbots rely on peers for survival

Design and modeling of safeguard control in microbial swarmbots exhibit collective survival. Bacteria confined in the microbial swarmbot can maintain a high local density and survive. Cells escaping the swarmbot will have a reduced density due to a larger extra-capsule environment. If their density drops below their survival threshold, they will die, leading to safeguard control. (credit: Shuqiang Huang et al./Molecular Systems Biology)

Duke University researchers have engineered microbes as “swarmbots” designed to only survive in a crowd.

The system could be used as a safeguard to stop genetically modified organisms (created with tools such as CRISPR) from escaping into the surrounding environment.

Collective survival

“Other labs have addressed this issue by making cells rely on unnatural amino acids for survival or by introducing a ‘kill switch’ that is activated by some chemical,” said Lingchong You, the Paul Ruffin Scarborough Associate Professor of Engineering at Duke University. “Ours is the first example that uses collective survival as a way of intrinsically realizing this safeguard.*

“In general, this concept does not depend on the use of antibiotics,” said You. “We’re using non-pathogenic E. coli, but we hope to demonstrate that the same concept can be established with a probiotic strain of bacteria.” Another method would be to insert a contained population of bacteria that could help the body respond to intruders.

“This is the foundation,” said You. “Once we’ve established the platform, then we have the freedom to introduce whatever proteins we choose and allow these cells to engage in many different applications.”

The approach could also be used to reliably program colonies of bacteria to respond to changes in their surrounding environment, such as releasing specific molecules on cue.

Terrorism implications

On Feb. 9, James R. Clapper, U.S. Director of National Intelligence warned that “given the broad distribution, low cost, and accelerated pace of development of this dual-use technology, its deliberate or unintentional misuse might lead to far-reaching economic and national security implications.” It’s not clear if the swarmbot system could address that concern.

Research in genome editing conducted by countries with different regulatory or ethical standards than those of Western countries probably increases the risk of the creation of potentially harmful biological agents or products. Given the broad distribution, low cost, and accelerated pace of development of this dual-use technology, its deliberate or unintentional misuse might lead to far-reaching economic and national security implications.

The swarmbot system is described online, February 29, 2016, in an open-access paper in Molecular Systems Biology.

This work was supported by the National Science Foundation, the National Institutes of Health, the Army Research Office, and a David and Lucile Packard Fellowship.

* In the experiment, You and his colleagues engineered a non-pathogenic strain of E. coli to produce a chemical called AHL. They also modified the cells so that, in high enough concentrations, AHL causes them to produce an antidote to antibiotics. When the population of E. coli is dense enough, the antidote keeps them alive, even in the presence of antibiotics that would otherwise kill them.

The researchers then confined a sufficiently large number of the bacteria to a capsule and bathed it in antibiotics. As long as the E. coli remained inside their container where their density was high, they all survived. But if individual bacteria escaped, they were quickly killed off by the antibiotic.


Duke University | Swarmbots

Abstract of Coupling spatial segregation with synthetic circuits to control bacterial survival

Engineered bacteria have great potential for medical and environmental applications. Fulfilling this potential requires controllability over engineered behaviors and scalability of the engineered systems. Here, we present a platform technology, microbial swarmbot, which employs spatial arrangement to control the growth dynamics of engineered bacteria. As a proof of principle, we demonstrated a safeguard strategy to prevent unintended bacterial proliferation. In particular, we adopted several synthetic gene circuits to program collective survival in Escherichia coli: the engineered bacteria could only survive when present at sufficiently high population densities. When encapsulated by permeable membranes, these bacteria can sense the local environment and respond accordingly. The cells inside the microbial swarmbot capsules will survive due to their high densities. Those escaping from a capsule, however, will be killed due to a decrease in their densities. We demonstrate that this design concept is modular and readily generalizable. Our work lays the foundation for engineering integrated and programmable control of hybrid biological–material systems for diverse applications.

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AI ‘alarmists’ nominated for 2015 ‘Luddite Award’

An 1844 engraving showing a post-1820s Jacquard loom (credit: public domain/Penny Magazine)

The Information Technology and Innovation Foundation (ITIF) today (Dec. 21) announced 10 nominees for its 2015 Luddite Award. The annual “honor” recognizes the year’s most egregious example of a government, organization, or individual stymieing the progress of technological innovation.

ITIF also opened an online poll and invited the public to help decide the “winner.” The result will be announced in late January.

The nominees include (in no specific order):

1. Alarmists, including respected luminaries such as Elon Musk, Stephen Hawking, and Bill Gates, touting an artificial- intelligence apocalypse.

2. Advocates, including Hawking and Noam Chomsky, seeking a ban on “killer robots.”

3. Vermont and other states limiting automatic license plate readers.

4. Europe, China, and others choosing taxi drivers over car-sharing passengers.

5. The U.S. paper industry opposing e-labeling.

6. California’s governor vetoing RFID tags in driver’s licenses.

7. Wyoming effectively outlawing citizen science.

8. The Federal Communications Commission limiting broadband innovation.

9. The Center for Food Safety fighting genetically improved food.

10. Ohio and other states banning red light cameras.

‘Paranoia about evil machines’

(credit: Paramount Pictures)

“Just as Ned Ludd wanted to smash mechanized looms and halt industrial progress in the 19th century, today’s neo-Luddites want to foil technological innovation to the detriment of the rest of society,” said Robert D. Atkinson, ITIF’s founder and president.

“If we want a world in which innovation thrives, then everyone’s New Year’s resolution should be to replace neo-Luddism with an attitude of risk-taking and faith in the future.”

Atkinson notes that “paranoia about evil machines has swirled around in popular culture for more than 200 years, and these claims continue to grip the popular imagination, in no small part because these apocalyptic ideas are widely represented in books, movies, and music.

“The last year alone saw blockbuster films with a parade of digital villains, such as Avengers: Age of Ultron, Ex Machina, and Terminator: Genisys.”

He also cites statements in Oxford professor Nick Bostrom’s book Superintelligence: Paths, Dangers, Strategies, “reflecting the general fear that ‘superintelligence’ in machines could outperform ‘the best human minds in every field, including scientific creativity, general wisdom and social skills.’ Bostrom argues that artificial intelligence will advance to a point where its goals are no longer compatible with that of humans and, as a result, superintelligent machines will seek to enslave or exterminate us.”

“Raising such sci-fi doomsday scenarios just makes it harder for the public, policymakers,  and scientists to support more funding for AI research, Atkinson concludes. “Indeed, continuing the negative campaign against artificial intelligence could potentially dry up funding for AI research, other than money for how to control, rather than enable AI. What legislator wants to be known as ‘the godfather of the technology that destroyed the human race’?”

Not mentioned in the ITIF statement is the recently announced non-profit “OpenAI” research company founded by Elon Musk and associates, committing $1 billion toward their goal to advance digital intelligence in the way that is most likely to benefit humanity as a whole.”

The 2014 Luddite Award winners

The winners last year: the states of Arizona, Michigan, New Jersey, and Texas, for taking action to prevent Tesla from opening stores in their states to sell cars directly to consumers. Other nominees included:

  • National Rifle Association (NRA) for its opposition to smart guns
  • “Stop Smart Meters” Seeks To Stop Smart Innovation in Meters and Cars
  • Free Press Lobbies for Rules to Stop Innovation in Broadband Networks
  • The Media and Pundits Claiming That “Robots” Are Killing Jobs.

 

 

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Musk, others commit $1 billion to non-profit AI research company to ‘benefit humanity’

(credit: OpenAI)

Elon Musk and associates announced OpenAI, a non-profit AI research company, on Friday (Dec. 11), committing $1 billion toward their goal to “advance digital intelligence in the way that is most likely to benefit humanity as a whole, unconstrained by a need to generate financial return.”

The funding comes from a group of tech leaders including Musk, Reid Hoffman, Peter Thiel, and Amazon Web Services, but the venture expects to only spend “a tiny fraction of this in the next few years.”

The founders note that it’s hard to predict how much AI could “damage society if built or used incorrectly” or how soon. But the hope is to have a leading research institution that can “prioritize a good outcome for all over its own self-interest … as broadly and evenly distributed as possible.”

Brains trust

OpenAI’s co-chairs are Musk, who is also the principal funder of Future of Life Institute, and Sam Altman, president of  venture-capital seed-accelerator firm Y Combinator, who is also providing funding.

“I think the best defense against the misuse of AI is to empower as many people as possible to have AI. If everyone has AI powers, then there’s not any one person or a small set of individuals who can have AI superpower.” — Elon Musk on Medium

The founders say the organization’s patents (if any) “will be shared with the world. We’ll freely collaborate with others across many institutions and expect to work with companies to research and deploy new technologies.”

OpenAI’s research director is machine learning expert Ilya Sutskever, formerly at Google, and its CTO is Greg Brockman, formerly the CTO of Stripe. The group’s other founding members are “world-class research engineers and scientists” Trevor Blackwell, Vicki Cheung, Andrej Karpathy, Durk Kingma, John Schulman, Pamela Vagata, and Wojciech Zaremba. Pieter Abbeel, Yoshua Bengio, Alan Kay, Sergey Levine, and Vishal Sikka are advisors to the group. The company will be based in San Francisco.

If I’m Dr. Evil and I use it, won’t you be empowering me?

“There are a few different thoughts about this. Just like humans protect against Dr. Evil by the fact that most humans are good, and the collective force of humanity can contain the bad elements, we think its far more likely that many, many AIs will work to stop the occasional bad actors than the idea that there is a single AI a billion times more powerful than anything else. If that one thing goes off the rails or if Dr. Evil gets that one thing and there is nothing to counteract it, then we’re really in a bad place.” — Sam Altman in an interview with Steven Levy on Medium.

The announcement follows recent announcements by Facebook to open-source the hardware design of its GPU-based “Big Sur” AI server (used for large-scale machine learning software to identify objects in photos and understand natural language, for example); by Google to open-source its TensorFlow machine-learning software; and by Toyota Corporation to invest $1 billion in a five-year private research effort in artificial intelligence and robotics technologies, jointly with Stanford University and MIT.

To follow OpenAI: @open_ai or info@openai.com

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Evidence that our Sun could release ‘superflares’ 1000x greater than previously recorded

What the Sun might look like if it were to produce a superflare. A large flaring coronal loop structure is shown towering over a solar active region. (credit: University of Warwick/Ronald Warmington)

Astrophysicists have discovered a stellar “superflare” on a star observed by NASA’s Kepler space telescope with wave patterns similar to those that have been observed in the Sun’s solar flares. (Superflares are flares that are thousands of times more powerful than those ever recorded on the Sun, and are frequently observed on some stars.)

The scientists found the evidence in the star KIC9655129 in the Milky Way. They suggest there are similarities between the superflare on KIC9655129 and the Sun’s solar flares, so the underlying physics of the flares might be the same.

Disastrous for life on Earth

Typical solar flares can have energies equivalent to a 100 million megaton bombs, but a superflare on our Sun could release energy equivalent to 100 billion megaton bombs, the scientists say.

The effects on the power grid in the U.S. would be similar to those resulting from a major cyberattack on America’s power grid, as described in the just-published book, Lights Out: A Cyberattack, A Nation Unprepared, Surviving the Aftermath.

The Earth’s communications and energy systems could be at serious risk of failing, the scientists note, and disastrous for life on Earth. Our GPS and radio communication systems could be severely disrupted and there could be large-scale power blackouts as a result of strong electrical currents being induced in power grids.

The evidence

Research co-author Anne-Marie Broomhall, PhD, from the University of Warwick explains: “When a flare occurs, we typically see a rapid increase in intensity followed by a gradual decline. Usually the decline phase is relatively smooth but occasionally there are noticeable bumps, which are termed ‘quasi-periodic pulsations’ or QPPs.”

The scientists used techniques called wavelet analysis and Monte Carlo modeling to assess the periodicity and statistical significance of these QPPs. The analysis revealed two significant periodicities, with less than a 1% probability that these pulsations would be observed by chance. The most plausible explanation for the presence of two independent periodicities: the QPPs were caused by magnetohydrodynamic (MHD) oscillations, which are also frequently observed in solar flares, the scientists say.

“This result is, therefore, an indication that the same physical processes are involved in both solar flares and stellar superflares. The latter finding supports the hypothesis that the Sun is able to produce a potentially devastating superflare.”

(Also see previous KurzweilAI coverage of this subject.)

The research is published by The Astrophysical Journal Letters and was funded by the European Research Council.

Abstract for A Multi-Period Oscillation In A Stellar Superflare

Flares that are orders of magnitude larger than the most energetic solar flares are routinely observed on Sun-like stars, raising the question of whether the same physical processes are responsible for both solar and stellar flares. In this Letter, we present a white-light stellar superflare on the star KIC 9655129, observed by NASA’s Kepler mission, with a rare multi-period quasi-periodic pulsation (QPP) pattern. Two significant periodic processes were detected using the wavelet and autocorrelation techniques, with periods of 78 ± 12 minutes and 32 ± 2 minutes. By comparing the phases and decay times of the two periodicities, the QPP signal was found to most likely be linear, suggesting that the two periodicities are independent, possibly corresponding either to different magnetohydrodynamic (MHD) modes of the flaring region or different spatial harmonics of the same mode. The presence of multiple periodicities is a good indication that the QPPs were caused by MHD oscillations and suggests that the physical processes in operation during stellar flares could be the same as those in solar flares.

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E-coli bacteria, found in some China farms and patients, cannot be killed with antiobiotic drug of last resort

Colistin antibiotic overused in farm animals in China apparently caused E-coli bacteria to become completely resistant to treatment; E-coli strain has already spread to Laos and Malaysia (credit: Yi-Yun Liu et al./Lancet Infect Dis)

Widespread E-coli bacteria that cannot be killed with the antiobiotic drug of last resort — colistin — have been found in samples taken from farm pigs, meat products, and a small number of patients in south China, including bacterial strains with epidemic potential, an international team of scientists revealed in a paper published Thursday Nov. 19 in the journal The Lancet Infectious Diseases.

The scientists in China, England, and the U.S. found a new gene, MCR-1, carried in E-coli bacteria strain SHP45. MCR-1 enables bacteria to be highly resistant to colistin and other polymyxins drugs.

“The emergence of the MCR-1 gene in China heralds a disturbing breach of the last group of antibiotics — polymixins — and an end to our last line of defense against infection,” said Professor Timothy Walsh, from the Cardiff University School of Medicine, who collaborated on this research with scientists from South China Agricultural University.

Walsh, an expert in antibiotic resistance, is best known for his discovery in 2011 of the NDM-1 disease-causing antibiotic-resistant superbug in New Delhi’s drinking water supply. “The rapid spread of similar antibiotic-resistant genes such as NDM-1 suggests that all antibiotics will soon be futile in the face of previously treatable gram-negative bacterial infections such as E.coli and salmonella,” he said.

Likely to spread worldwide; already found in Laos and Malaysia

The MCR-1 gene was found on plasmids — mobile DNA that can be easily copied and transferred between different bacteria, suggesting an alarming potential to spread and diversify between different bacterial populations.

Structure of plasmid pHNSHP45 carrying MCR-1 from Escherichia coli strain SHP45 (credit: Yi-Yun Liu et al./Lancet Infect Dis)

“We now have evidence to suggest that MCR-1-positive E.coli has spread beyond China, to Laos and Malaysia, which is deeply concerning,” said Walsh.  “The potential for MCR-1 to become a global issue will depend on the continued use of polymixin antibiotics, such as colistin, on animals, both in and outside China; the ability of MCR-1 to spread through human strains of E.coli; and the movement of people across China’s borders.”

“MCR-1 is likely to spread to the rest of the world at an alarming rate unless we take a globally coordinated approach to combat it. In the absence of new antibiotics against resistant gram-negative pathogens, the effect on human health posed by this new gene cannot be underestimated.”

“Of the top ten largest producers of colistin for veterinary use, one is Indian, one is Danish, and eight are Chinese,” The Lancet Infectious Diseases notes. “Asia (including China) makes up 73·1% of colistin production with 28·7% for export including to Europe.29 In 2015, the European Union and North America imported 480 tonnes and 700 tonnes, respectively, of colistin from China.”

Urgent need for coordinated global action

“Our findings highlight the urgent need for coordinated global action in the fight against extensively resistant and pan-resistant gram-negative bacteria,” the journal paper concludes.

“The implications of this finding are enormous,” an associated editorial comment to the The Lancet Infectious Diseases paper stated. “We must all reiterate these appeals and take them to the highest levels of government or face increasing numbers of patients for whom we will need to say, ‘Sorry, there is nothing I can do to cure your infection.’”

Margaret Chan, MD, Director-General of the World Health Organization, warned in 2011 that “the world is heading towards a post-antibiotic era, in which many common infections will no longer have a cure and, once again, kill unabated.”

“Although in its 2012 World Health Organization Advisory Group on Integrated Surveillance of Antimicrobial Resistance (AGISAR) report the WHO concluded that colistin should be listed under those antibiotics of critical importance, it is regrettable that in the 2014 Global Report on Surveillance, the WHO did not to list any colistin-resistant bacteria as part of their ‘selected bacteria of international concern,’” The Lancet Infectious Diseases paper says, reflecting WHO’s inaction in Ebola-stricken African countries, as noted last September by the international medical humanitarian organization Médecins Sans Frontières.

Funding for the E-coli bacteria study was provided by the Ministry of Science and Technology of China and National Natural Science Foundation of China.

Abstract of Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study

Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via
horizontal gene transfer. During a routine surveillance project on antimicrobial resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae.

The mcr-1 gene in E coli strain SHP45 was identified by whole plasmid sequencing and subcloning. MCR-1 mechanistic studies were done with sequence comparisons, homology modelling, and electrospray ionisation mass spectrometry. The prevalence of mcr-1 was investigated in E coli and Klebsiella pneumoniae strains collected from five provinces between April, 2011, and November, 2014. The ability of MCR-1 to confer polymyxin resistance in vivo was examined in a murine thigh model.

Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10−1 to 10−3 cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa. In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011–14, and 16 (1%) of 1322 samples from inpatients with infection.

The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria.

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E-coli bacteria, found in some China farms and patients, cannot be killed with antiobiotic drug of last resort

Colistin antibiotic overused in farm animals in China apparently caused E-coli bacteria to become completely resistant to treatment; E-coli strain has already spread to Laos and Malaysia (credit: Yi-Yun Liu et al./Lancet Infect Dis)

Widespread E-coli bacteria that cannot be killed with the antiobiotic drug of last resort — colistin — have been found in samples taken from farm pigs, meat products, and a small number of patients in south China, including bacterial strains with epidemic potential, an international team of scientists revealed in a paper published Thursday Nov. 19 in the journal The Lancet Infectious Diseases.

The scientists in China, England, and the U.S. found a new gene, MCR-1, carried in E-coli bacteria strain SHP45. MCR-1 enables bacteria to be highly resistant to colistin and other polymyxins drugs.

“The emergence of the MCR-1 gene in China heralds a disturbing breach of the last group of antibiotics — polymixins — and an end to our last line of defense against infection,” said Professor Timothy Walsh, from the Cardiff University School of Medicine, who collaborated on this research with scientists from South China Agricultural University.

Walsh, an expert in antibiotic resistance, is best known for his discovery in 2011 of the NDM-1 disease-causing antibiotic-resistant superbug in New Delhi’s drinking water supply. “The rapid spread of similar antibiotic-resistant genes such as NDM-1 suggests that all antibiotics will soon be futile in the face of previously treatable gram-negative bacterial infections such as E.coli and salmonella,” he said.

Likely to spread worldwide; already found in Laos and Malaysia

The MCR-1 gene was found on plasmids — mobile DNA that can be easily copied and transferred between different bacteria, suggesting an alarming potential to spread and diversify between different bacterial populations.

Structure of plasmid pHNSHP45 carrying MCR-1 from Escherichia coli strain SHP45 (credit: Yi-Yun Liu et al./Lancet Infect Dis)

“We now have evidence to suggest that MCR-1-positive E.coli has spread beyond China, to Laos and Malaysia, which is deeply concerning,” said Walsh.  “The potential for MCR-1 to become a global issue will depend on the continued use of polymixin antibiotics, such as colistin, on animals, both in and outside China; the ability of MCR-1 to spread through human strains of E.coli; and the movement of people across China’s borders.”

“MCR-1 is likely to spread to the rest of the world at an alarming rate unless we take a globally coordinated approach to combat it. In the absence of new antibiotics against resistant gram-negative pathogens, the effect on human health posed by this new gene cannot be underestimated.”

“Of the top ten largest producers of colistin for veterinary use, one is Indian, one is Danish, and eight are Chinese,” The Lancet Infectious Diseases notes. “Asia (including China) makes up 73·1% of colistin production with 28·7% for export including to Europe.29 In 2015, the European Union and North America imported 480 tonnes and 700 tonnes, respectively, of colistin from China.”

Urgent need for coordinated global action

“Our findings highlight the urgent need for coordinated global action in the fight against extensively resistant and pan-resistant gram-negative bacteria,” the journal paper concludes.

“The implications of this finding are enormous,” an associated editorial comment to the The Lancet Infectious Diseases paper stated. “We must all reiterate these appeals and take them to the highest levels of government or face increasing numbers of patients for whom we will need to say, ‘Sorry, there is nothing I can do to cure your infection.’”

Margaret Chan, MD, Director-General of the World Health Organization, warned in 2011 that “the world is heading towards a post-antibiotic era, in which many common infections will no longer have a cure and, once again, kill unabated.”

“Although in its 2012 World Health Organization Advisory Group on Integrated Surveillance of Antimicrobial Resistance (AGISAR) report the WHO concluded that colistin should be listed under those antibiotics of critical importance, it is regrettable that in the 2014 Global Report on Surveillance, the WHO did not to list any colistin-resistant bacteria as part of their ‘selected bacteria of international concern,’” The Lancet Infectious Diseases paper says, reflecting WHO’s inaction in Ebola-stricken African countries, as noted last September by the international medical humanitarian organization Médecins Sans Frontières.

Funding for the E-coli bacteria study was provided by the Ministry of Science and Technology of China and National Natural Science Foundation of China.

Abstract of Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study

Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via
horizontal gene transfer. During a routine surveillance project on antimicrobial resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae.

The mcr-1 gene in E coli strain SHP45 was identified by whole plasmid sequencing and subcloning. MCR-1 mechanistic studies were done with sequence comparisons, homology modelling, and electrospray ionisation mass spectrometry. The prevalence of mcr-1 was investigated in E coli and Klebsiella pneumoniae strains collected from five provinces between April, 2011, and November, 2014. The ability of MCR-1 to confer polymyxin resistance in vivo was examined in a murine thigh model.

Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10−1 to 10−3 cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa. In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011–14, and 16 (1%) of 1322 samples from inpatients with infection.

The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria.

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This app lets autonomous video drones with facial recognition target persons

Creating a selfie video with a drone and an app (credit: Neurala)

Robotics company Neurala has combined facial-recognition and drone-control mobile software in an iOS/Android app called “Selfie Dronie” that enables low-cost Parrot Bebop and Bebop 2 drones to take hands-free videos and follow a subject autonomously.

To create a video, you simply select the person or object and you’re done. The drone then flies an arc around the subject to take a video selfie (it moves with the person). Or it zooms upward for a dramatic aerial shot in “dronie” mode.


Neurela | This video demonstrates Neurela’s target-following technology

Basically, the app replaces remote-control gadgets and controlling via GPS on cell phones. Instead, once the target person is designated, the drone operates autonomously.

Neurala explains that its Neurala Intelligence Engine (NIE) can immediately learn to recognize an object using an ordinary camera. Then, as the object moves, Neurala’s deep learning algorithms learn more about the object in real time and in different environments, and by comparing these observations to other things it has learned in the past — going beyond current deep-learning visual processing, which requires training first.

Based on Mars rover technology

Neurala says NASA funded Neurela in October to commercialize its autonomous navigation, object recognition, and obstacle avoidance software developed for planetary exploration robots such as Curiosity rover, and apply it in real-world situations on Earth for self-driving cars, home robots, and autonomous drones.

Neurela says what makes its software unique is its use of deep learning and passive sensors, instead of “expensive and power-hungry active systems,” such as radar and LIDAR, used in most prototype self-driving vehicles.

Of course, it’s a small step from this technology to surveillance drones with facial recognition and autonomous weaponized unmanned aerial vehicles (see “The proposed ban on offensive autonomous weapons is unrealistic and dangerous” and “Why we really should ban autonomous weapons: a response“), especially given the recent news in Paris and Brussels and current terrorist threats directed to the U.S. and other countries.

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Mass extinctions linked to comet and asteroid showers

Mass extinctions occurring over the past 260 million years were likely caused by comet and asteroid showers, a new study concludes. An artist’s illustration of a major asteroid impact on Earth. (credit: NASA/Don Davis)

Mass extinctions occurring over the past 260 million years were likely caused by comet and asteroid showers, scientists conclude in a new study published in an open-access paper in Monthly Notices of the Royal Astronomical Society.

For more than 30 years, scientists have argued about a controversial hypothesis relating to periodic mass extinctions and impact craters — caused by comet and asteroid showers — on Earth.

In their MNRAS paper, Michael Rampino, a New York University geologist, and Ken Caldeira, a scientist in the Carnegie Institution’s Department of Global Ecology, offer new support linking the age of these craters with recurring mass extinctions of life every 26 million years, including the demise of dinosaurs.

This cycle has been linked to periodic motion of the sun and planets through the dense mid-plane of our galaxy. Scientists have theorized that gravitational perturbations of the distant Oort comet cloud that surrounds the sun lead to periodic comet showers in the inner solar system, where some comets strike the Earth.

Crater formation rate per million years, with eight significant extinction events shown with solid arrows and two potential extinction events shown with broken arrows (credit: Michael R. Rampino and Ken Caldeira/MNRAS)

To test their hypothesis, Rampino and Caldeira performed time-series analyses of impacts and extinctions using newly available data offering more accurate age estimates. “The correlation between the formation of these impacts and extinction events over the past 260 million years is striking and suggests a cause-and-effect relationship,” says Rampino.

The sinkholes clustered around the trough of the Chicxulub crater suggest a prehistoric oceanic basin in the depression left by the impact. (credit: NASA)

One of the craters considered in the study is the large (180 km diameter) Chicxulub impact structure in the Yucatan, which dates at about 65 million years ago — the time of a great mass extinction that included the dinosaurs. And five out of the six largest impact craters of the last 260 million years on earth correlate with mass extinction events.

Abstract of Periodic impact cratering and extinction events over the last 260 million years

The claims of periodicity in impact cratering and biological extinction events are controversial. A newly revised record of dated impact craters has been analyzed for periodicity, and compared with the record of extinctions over the past 260 Myr. A digital circular spectral analysis of 37 crater ages (ranging in age from 15 to 254 Myr ago) yielded evidence for a significant 25.8 ± 0.6 Myr cycle. Using the same method, we found a significant 27.0 ± 0.7 Myr cycle in the dates of the eight recognized marine extinction events over the same period. The cycles detected in impacts and extinctions have a similar phase. The impact crater dataset shows 11 apparent peaks in the last 260 Myr, at least 5 of which correlate closely with significant extinction peaks. These results suggest that the hypothesis of periodic impacts and extinction events is still viable.

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Move over, autonomous AI weapons, there’s a new risk in town: ‘gene drives’

Wyss Institute scientists believe that synthetic gene drives, if researched responsibly, might be used in the future to render mosquito populations unable to transmit malaria (credit: CDC)

An international group of 26 experts, including prominent genetic engineers and fruit fly geneticists, has unanimously recommended a series of preemptive measures to safeguard gene drive research from accidental (or intentional) release from laboratories.

RNA-guided gene drives are genetic elements — found naturally in the genomes of most of the world’s organisms — that increase the chance of the gene they carry being passed on to all offspring. So  they can quickly spread through populations if not controlled.

Looking to these natural systems, researchers around the world, including some  scientists, are developing synthetic gene drives that could one day be leveraged by humans to purposefully alter the traits of wild populations of organisms to prevent disease transmission and eradicate invasive species.

What could possibly go wrong?

These synthetic gene drives, designed using an RNA-guided gene editing system called CRISPR, could one day improve human health and the environment by preventing mosquitoes and ticks from spreading diseases such as malaria and Lyme; by promoting sustainable agriculture through control of crop pests without the use of toxic pesticides and herbicides; and by protecting at-risk ecosystems from the spread of destructive, invasive species such as rats or cane toads.

Most genome alterations don’t persist in nature. Only 50 percent of transgenic mosquito offspring (left) will carry the altered gene, so it may persist at low frequency or go instinct. With gene drive (right), using CRISPR/Cas9, all of the offspring will carry the altered gene and will be inherited through the population. (credit: adapted from Wyss Institute video)

However, the development of RNA-guided gene drive technology calls for enhanced safety measures. That’s because its capability to also affect shared ecosystems if organisms containing synthetic gene drives are accidentally or deliberately released from a laboratory. This potential risk is especially relevant with highly mobile species such as fruit flies or mosquitoes.

Guidelines available

“One of the great successes of engineering is the development of safety features, such as the rounding of sharp corners on objects and the invention of airbags for cars, and in biological engineering we want to emulate the process of designing safety features in ways relevant to the technologies we develop,” said Wyss Core Faculty member George Church, Ph.D., who leads the Synthetic Biology Platform at the Wyss Institute. Church is also the Robert Winthrop Professor of Genetics at Harvard Medical School and Professor of Health Sciences and Technology at Harvard and MIT.

At the Wyss Institute, enhanced protocols for safely and securely researching emerging biotechnologies, including RNA–guided gene drives, have already been formally implemented. The safeguards were put in place proactively, step–by–step, in direct parallel with the development of the first RNA-guided gene drives at the Wyss Institute.

The working documents have been made publicly available by the Institute to encourage widespread adoption of multi-tier confinement and risk assessment procedures. Church was instrumental in the design of the enhanced biosafety and biosecurity protocols.

Now, research teams from the Wyss Institute and University of California, San Diego — the only two groups to have published work on RNA-guided CRISPR gene drives — have proactively assembled an international group of 26 experts, including prominent genetic engineers and fruit fly geneticists, to unanimously recommend a series of preemptive measures to safeguard gene drive research.

Open-access research recommended

Led by Wyss Institute Technology Development Fellow, Kevin Esvelt, Ph.D., and UC San Diego Professor of Cell and Developmental Biology Ethan Bier, Ph.D., the 26 authors of this consensus recommendation, which is published online in Science Express journal and includes representatives from every major group known to be working on gene drives, calls for all researchers to use multiple confinement strategies in order to prevent the accidental alteration of wild populations.

The group also provides explicit recommended guidelines for regulatory authorities evaluating proposed new work. And Esvelt and others are hopeful that the field of gene drive research is so nascent that it may be possible to build a community of scientists that share their research with the public throughout the development process.

“This would promote collaboration and avoid needless duplication of efforts among different research groups while allowing diverse voices to help guide the development of a technology that could improve our shared world,” said Esvelt. “And eventually, it might inspire a similar shift towards full transparency in other scientific fields of collective public importance.”

“The scientific community has a responsibility to the public and to the environment to constantly assess how new biotechnologies could potentially impact our world,” said Wyss Institute Founding Director Donald E. Ingber, M.D., Ph.D.

“This proactive consensus recommendation — reached in an extraordinary demonstration of the power of scientific collaboration over competition — provides concrete, useful guidelines for safeguarding our shared ecosystem while ensuring that remarkable breakthroughs, such as synthetic gene drives, can be applied to their full potential for the greater good.”


Wyss Institute at Harvard University | CRISPER-Cas9: Gene Drive

This animation explains how gene drives could one day be used to spread gene alterations through targeted wild populations over many generations, for purposes such as preventing spread of insect-borne disease and controlling invasive plant species. To ensure gene drives have the potential to be used for the greater good in the future, Wyss Institute Technology Development Fellow Kevin Esvelt, Ph.D., has co-led an international consensus of 26 scientists to recommend safeguards to prevent synthetic gene drive research from having any accidental impacts on the world’s shared ecosystems.

Abstract of A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells

INTRODUCTION: Administering vaccines through nonmucosal routes often leads to poor protection against mucosal pathogens, presumably because such vaccines do not generate memory lymphocytes that migrate to mucosal surfaces. Although mucosal vaccination induces mucosa-tropic memory lymphocytes, few mucosal vaccines are used clinically; live vaccine vectors pose safety risks, whereas killed pathogens or molecular antigens are usually weak immunogens when applied to intact mucosa. Adjuvants can boost immunogenicity; however, most conventional mucosal adjuvants have unfavorable safety profiles. Moreover, the immune mechanisms of protection against many mucosal infections are poorly understood.

RATIONALE: One case in point is Chlamydia trachomatis (Ct), a sexually transmitted intracellular bacterium that infects >100 million people annually. Mucosal Ct infections can cause female infertility and ectopic pregnancies. Ct is also the leading cause of preventable blindness in developing countries and induces pneumonia in infants. No approved vaccines exist to date. Here, we describe a Ct vaccine composed of ultraviolet light–inactivated Ct (UV-Ct) conjugated to charge-switching synthetic adjuvant nanoparticles (cSAPs). After immunizing mice with live Ct, UV-Ct, or UV-Ct–cSAP conjugates, we characterized mucosal immune responses to uterine Ct rechallenge and dissected the underlying cellular mechanisms.

RESULTS: In previously uninfected mice, Ct infection induced protective immunity that depended on CD4 T cells producing the cytokine interferon-γ, whereas uterine exposure to UV-Ct generated tolerogenic Ct-specific regulatory T cells, resulting in exacerbated bacterial burden upon Ct rechallenge. In contrast, mucosal immunization with UV-Ct–cSAP elicited long-lived protection. This differential effect of UV-Ct–cSAP versus UV-Ct was because the former was presented by immunogenic CD11b+CD103– dendritic cells (DCs), whereas the latter was presented by tolerogenic CD11b–CD103+ DCs. Intrauterine or intranasal vaccination, but not subcutaneous vaccination, induced genital protection in both conventional and humanized mice. Regardless of vaccination route, UV-Ct–cSAP always evoked a robust systemic memory T cell response. However, only mucosal vaccination induced a wave of effector T cells that seeded the uterine mucosa during the first week after vaccination and established resident memory T cells (TRM cells). Without TRM cells, mice were suboptimally protected, even when circulating memory cells were abundant. Optimal Ct clearance required both early uterine seeding by TRM cells and infection-induced recruitment of a second wave of circulating memory cells.

CONCLUSIONS: Mucosal exposure to both live Ct and inactivated UV-Ct induces antigen-specific CD4 T cell responses. While immunogenic DCs present the former to promote immunity, the latter is instead targeted to tolerogenic DCs that exacerbate host susceptibility to Ct infection. By combining UV-Ct with cSAP nanocarriers, we have redirected noninfectious UV-Ct to immunogenic DCs and achieved long-lived protection. This protective vaccine effect depended on the synergistic action of two memory T cell subsets with distinct differentiation kinetics and migratory properties. The cSAP technology offers a platform for efficient mucosal immunization that may also be applicable to other mucosal pathogens.