Tag Archives: MIT

Of sleep, electric sheep, and thousands of artificial synapses on a chip

A close-up view of a new neuromorphic “brain-on-a-chip” that includes tens of thousands of memristors, or memory transistors. Credit: Peng Lin Courtesy: MIT

It’s hard to believe that a brain-on-a-chip might need sleep but that seems to be the case as far as the US Dept. of Energy’s Los Alamos National Laboratory is concerned. Before pursuing that line of thought, here’s some work from the Massachusetts Institute of Technology (MIT) involving memristors and a brain-on-a-chip. From a June 8, 2020 news item on ScienceDaily,

MIT engineers have designed a “brain-on-a-chip,” smaller than a piece of confetti, that is made from tens of thousands of artificial brain synapses known as memristors — silicon-based components that mimic the information-transmitting synapses in the human brain.

The researchers borrowed from principles of metallurgy to fabricate each memristor from alloys of silver and copper, along with silicon. When they ran the chip through several visual tasks, the chip was able to “remember” stored images and reproduce them many times over, in versions that were crisper and cleaner compared with existing memristor designs made with unalloyed elements.

Their results, published today in the journal Nature Nanotechnology, demonstrate a promising new memristor design for neuromorphic devices — electronics that are based on a new type of circuit that processes information in a way that mimics the brain’s neural architecture. Such brain-inspired circuits could be built into small, portable devices, and would carry out complex computational tasks that only today’s supercomputers can handle.

This ‘metallurgical’ approach differs somewhat from the protein nanowire approach used by the University of Massachusetts at Amherst team mentioned in my June 15, 2020 posting. Scientists are pursuing multiple pathways and we may find that we arrive with not ‘a single artificial brain but with many types of artificial brains.

A June 8, 2020 MIT news release (also on EurekAlert) provides more detail about this brain-on-a-chip,

“So far, artificial synapse networks exist as software. We’re trying to build real neural network hardware for portable artificial intelligence systems,” says Jeehwan Kim, associate professor of mechanical engineering at MIT. “Imagine connecting a neuromorphic device to a camera on your car, and having it recognize lights and objects and make a decision immediately, without having to connect to the internet. We hope to use energy-efficient memristors to do those tasks on-site, in real-time.”

Wandering ions

Memristors, or memory transistors [Note: Memristors are usually described as memory resistors; this is the first time I’ve seen ‘memory transistor’], are an essential element in neuromorphic computing. In a neuromorphic device, a memristor would serve as the transistor in a circuit, though its workings would more closely resemble a brain synapse — the junction between two neurons. The synapse receives signals from one neuron, in the form of ions, and sends a corresponding signal to the next neuron.

A transistor in a conventional circuit transmits information by switching between one of only two values, 0 and 1, and doing so only when the signal it receives, in the form of an electric current, is of a particular strength. In contrast, a memristor would work along a gradient, much like a synapse in the brain. The signal it produces would vary depending on the strength of the signal that it receives. This would enable a single memristor to have many values, and therefore carry out a far wider range of operations than binary transistors.

Like a brain synapse, a memristor would also be able to “remember” the value associated with a given current strength, and produce the exact same signal the next time it receives a similar current. This could ensure that the answer to a complex equation, or the visual classification of an object, is reliable — a feat that normally involves multiple transistors and capacitors.

Ultimately, scientists envision that memristors would require far less chip real estate than conventional transistors, enabling powerful, portable computing devices that do not rely on supercomputers, or even connections to the Internet.

Existing memristor designs, however, are limited in their performance. A single memristor is made of a positive and negative electrode, separated by a “switching medium,” or space between the electrodes. When a voltage is applied to one electrode, ions from that electrode flow through the medium, forming a “conduction channel” to the other electrode. The received ions make up the electrical signal that the memristor transmits through the circuit. The size of the ion channel (and the signal that the memristor ultimately produces) should be proportional to the strength of the stimulating voltage.

Kim says that existing memristor designs work pretty well in cases where voltage stimulates a large conduction channel, or a heavy flow of ions from one electrode to the other. But these designs are less reliable when memristors need to generate subtler signals, via thinner conduction channels.

The thinner a conduction channel, and the lighter the flow of ions from one electrode to the other, the harder it is for individual ions to stay together. Instead, they tend to wander from the group, disbanding within the medium. As a result, it’s difficult for the receiving electrode to reliably capture the same number of ions, and therefore transmit the same signal, when stimulated with a certain low range of current.

Borrowing from metallurgy

Kim and his colleagues found a way around this limitation by borrowing a technique from metallurgy, the science of melding metals into alloys and studying their combined properties.

“Traditionally, metallurgists try to add different atoms into a bulk matrix to strengthen materials, and we thought, why not tweak the atomic interactions in our memristor, and add some alloying element to control the movement of ions in our medium,” Kim says.

Engineers typically use silver as the material for a memristor’s positive electrode. Kim’s team looked through the literature to find an element that they could combine with silver to effectively hold silver ions together, while allowing them to flow quickly through to the other electrode.

The team landed on copper as the ideal alloying element, as it is able to bind both with silver, and with silicon.

“It acts as a sort of bridge, and stabilizes the silver-silicon interface,” Kim says.

To make memristors using their new alloy, the group first fabricated a negative electrode out of silicon, then made a positive electrode by depositing a slight amount of copper, followed by a layer of silver. They sandwiched the two electrodes around an amorphous silicon medium. In this way, they patterned a millimeter-square silicon chip with tens of thousands of memristors.

As a first test of the chip, they recreated a gray-scale image of the Captain America shield. They equated each pixel in the image to a corresponding memristor in the chip. They then modulated the conductance of each memristor that was relative in strength to the color in the corresponding pixel.

The chip produced the same crisp image of the shield, and was able to “remember” the image and reproduce it many times, compared with chips made of other materials.

The team also ran the chip through an image processing task, programming the memristors to alter an image, in this case of MIT’s Killian Court, in several specific ways, including sharpening and blurring the original image. Again, their design produced the reprogrammed images more reliably than existing memristor designs.

“We’re using artificial synapses to do real inference tests,” Kim says. “We would like to develop this technology further to have larger-scale arrays to do image recognition tasks. And some day, you might be able to carry around artificial brains to do these kinds of tasks, without connecting to supercomputers, the internet, or the cloud.”

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

Alloying conducting channels for reliable neuromorphic computing by Hanwool Yeon, Peng Lin, Chanyeol Choi, Scott H. Tan, Yongmo Park, Doyoon Lee, Jaeyong Lee, Feng Xu, Bin Gao, Huaqiang Wu, He Qian, Yifan Nie, Seyoung Kim & Jeehwan Kim. Nature Nanotechnology (2020 DOI: https://doi.org/10.1038/s41565-020-0694-5 Published: 08 June 2020

This paper is behind a paywall.

Electric sheep and sleeping androids

I find it impossible to mention that androids might need sleep without reference to Philip K. Dick’s 1968 novel, “Do Androids Dream of Electric Sheep?”; its Wikipedia entry is here.

June 8, 2020 Intelligent machines of the future may need to sleep as much as we do. Intelligent machines of the future may need to sleep as much as we do. Courtesy: Los Alamos National Laboratory

As it happens, I’m not the only one who felt the need to reference the novel, from a June 8, 2020 news item on ScienceDaily,

No one can say whether androids will dream of electric sheep, but they will almost certainly need periods of rest that offer benefits similar to those that sleep provides to living brains, according to new research from Los Alamos National Laboratory.

“We study spiking neural networks, which are systems that learn much as living brains do,” said Los Alamos National Laboratory computer scientist Yijing Watkins. “We were fascinated by the prospect of training a neuromorphic processor in a manner analogous to how humans and other biological systems learn from their environment during childhood development.”

Watkins and her research team found that the network simulations became unstable after continuous periods of unsupervised learning. When they exposed the networks to states that are analogous to the waves that living brains experience during sleep, stability was restored. “It was as though we were giving the neural networks the equivalent of a good night’s rest,” said Watkins.

A June 8, 2020 Los Alamos National Laboratory (LANL) news release (also on EurekAlert), which originated the news item, describes the research team’s presentation,

The discovery came about as the research team worked to develop neural networks that closely approximate how humans and other biological systems learn to see. The group initially struggled with stabilizing simulated neural networks undergoing unsupervised dictionary training, which involves classifying objects without having prior examples to compare them to.

“The issue of how to keep learning systems from becoming unstable really only arises when attempting to utilize biologically realistic, spiking neuromorphic processors or when trying to understand biology itself,” said Los Alamos computer scientist and study coauthor Garrett Kenyon. “The vast majority of machine learning, deep learning, and AI researchers never encounter this issue because in the very artificial systems they study they have the luxury of performing global mathematical operations that have the effect of regulating the overall dynamical gain of the system.”

The researchers characterize the decision to expose the networks to an artificial analog of sleep as nearly a last ditch effort to stabilize them. They experimented with various types of noise, roughly comparable to the static you might encounter between stations while tuning a radio. The best results came when they used waves of so-called Gaussian noise, which includes a wide range of frequencies and amplitudes. They hypothesize that the noise mimics the input received by biological neurons during slow-wave sleep. The results suggest that slow-wave sleep may act, in part, to ensure that cortical neurons maintain their stability and do not hallucinate.

The groups’ next goal is to implement their algorithm on Intel’s Loihi neuromorphic chip. They hope allowing Loihi to sleep from time to time will enable it to stably process information from a silicon retina camera in real time. If the findings confirm the need for sleep in artificial brains, we can probably expect the same to be true of androids and other intelligent machines that may come about in the future.

Watkins will be presenting the research at the Women in Computer Vision Workshop on June 14 [2020] in Seattle.

The 2020 Women in Computer Vition Workshop (WICV) website is here. As is becoming standard practice for these times, the workshop was held in a virtual environment. Here’s a link to and a citation for the poster presentation paper,

Using Sinusoidally-Modulated Noise as a Surrogate for Slow-Wave Sleep to
Accomplish Stable Unsupervised Dictionary Learning in a Spike-Based Sparse Coding Model
by Yijing Watkins, Edward Kim, Andrew Sornborger and Garrett T. Kenyon. Women in Computer Vision Workshop on June 14, 2020 in Seattle, Washington (state)

This paper is open access for now.

Harvard professor and leader in nanoscale electronics charged with making false statements about Chinese funding

I may be mistaken but the implication seems to be that Charles M. Lieber’s lies (he was charged today, January 28, 2020 ) are the ‘tip of the iceberg’ of a very large problem. Ellen Barry’s January 28, 2020 article for the New York Times outlines at least part of what the US government is doing to discover and ultimately discourage the theft of biomedical research from US laboratories.

Dr. Lieber, a leader in the field of nanoscale electronics, was one of three Boston-area scientists accused on Tuesday [January 28, 2020] of working on behalf of China. His case involves work with the Thousand Talents Program, a state-run program that seeks to draw talent educated in other countries.

American officials are investigating hundreds of cases of suspected theft of intellectual property by visiting scientists, nearly all of them Chinese nationals or of Chinese descent. Some are accused of obtaining patents in China based on work that is funded by the United States government, and others of setting up laboratories in China that secretly duplicated American research.

Dr. Lieber, who was arrested on Tuesday [January 28, 2020], stands out among the accused scientists, because he is neither Chinese nor of Chinese descent. …

Lieber is the Chair of Harvard’s Department of Chemistry and Chemical Biology and much more, according to his Wikipedia entry (Note: Links have been removed),

Charles M. Lieber (born 1959) is an American chemist and pioneer in the field of nanoscience and nanotechnology. In 2011, Lieber was recognized by Thomson Reuters as the leading chemist in the world for the decade 2000-2010 based on the impact of his scientific publications.[1] Lieber has published over 400 papers in peer-reviewed scientific journals and has edited and contributed to many books on nanoscience.[2] He is the principal inventor on over fifty issued US patents and applications, and founded the nanotechnology company Nanosys in 2001 and Vista Therapeutics in 2007.[3] He is known for his contributions to the synthesis, assembly and characterization of nanoscale materials and nanodevices, the application of nanoelectronic devices in biology, and as a mentor to numerous leaders in nanoscience.[4] Thompson Reuters predicted Lieber to be a recipient of the 2008 Nobel Prize in Chemistry [to date, January 28, 2020, Lieber has not received a Nobel prize].

Should you search Charles Lieber or Charles M. Lieber on this blog’s search engine, you will find a number of postings about his and his students’ work dating from 2012 to as recently as November 15, 2019.

Here’s another example from Barry’s January 28, 2020 article for the New York Times which illustrates just how shocking this is (Note: Links have been removed),

In 2017 he was named a University Professor, Harvard’s highest faculty rank, one of only 26 professors to hold that status. The same year, he earned the National Institutes of Health Director’s Pioneer Award for inventing syringe-injectable mesh electronics that can integrate with the brain.

Harvard’s president at the time, Drew G. Faust, called him “an extraordinary scientist whose work has transformed nanoscience and nanotechnology and has led to a remarkable range of valuable applications that improve the quality of people’s lives.”

Here’s a bit more about the Chinese program that Lieber is affiliated with,

Launched in 2008, its [China] Thousand Talents Program is an effort to recruit Chinese and foreign academics and entrepreneurs. According to a report in the China Daily, new recruits receive 1 million yuan, or about $146,000, from the central government, and a pledge of 10 million yuan for their ongoing research from the Chinese Academy of Sciences.

The recruitment flows both ways. Researchers of Chinese descent make up nearly half of the work force in American research laboratories, in part because American-born scientists are drawn to the private sector and less interested in academic careers.

I encourage you to read Barry’s entire article. It is jaw-dropping and, where Lieber is concerned, sad. It’s beginning to look like US universities are corrupt. The Jeffrey Epstein (a wealthy and convicted sexual predator and more) connection to the Massachusetts Institute of Technology, which led to the resignation of a prominent faculty member (Sept. 19, 2019 article by Anna North for Vox.com), and the Fall 2019 cheating scandal (gaining admission to big name educational institutions by paying someone other than the student to take exams, among many other schemes) suggest a reckoning might be in order.

ETA January 28, 2020 at 1645 hours: I found a January 28, 2020 article by Antonio Regalado for the MIT Technology Review which provides a few more details about Lieber’s situation,

Big money: According to the charging document, Lieber, starting in 2011,  agreed to help set up a research lab at the Wuhan University of Technology and “make strategic visionary and creative research proposals” so that China could do cutting-edge science.

He was well paid for it. Lieber earned a salary when he visited China worth up to $50,000 per month, as well as $150,000 a year in expenses in addition to research funds. According to the complaint, he got paid by way of a Chinese bank account but also was known to send emails asking for cash instead.

Harvard eventually wised up to the existence of a Wuhan lab using its name and logo, but when administrators confronted Lieber, he lied and said he didn’t know about a formal joint program, according to the government complaint.

I imagine the money paid by the Chinese government is in addition to Lieber’s Harvard salary (no doubt a substantial one especially since he’s chair of his department and one of a select number of Harvard’s University Professors) and in addition to any other deals he might have on the side.

Sonifying proteins to make music and brand new proteins

Markus Buehler at the Massachusetts Institute of Technology (MIT) has been working with music and science for a number of years. My December 9, 2011 posting, Music, math, and spiderwebs, was the first one here featuring his work. My November 28, 2012 posting, Producing stronger silk musically, was a followup to Buehler’s previous work.

A June 28, 2019 news item on Azonano provides a recent update,

Composers string notes of different pitch and duration together to create music. Similarly, cells join amino acids with different characteristics together to make proteins.

Now, researchers have bridged these two seemingly disparate processes by translating protein sequences into musical compositions and then using artificial intelligence to convert the sounds into brand-new proteins. …

Caption: Researchers at MIT have developed a system for converting the molecular structures of proteins, the basic building blocks of all living beings, into audible sound that resembles musical passages. Then, reversing the process, they can introduce some variations into the music and convert it back into new proteins never before seen in nature. Credit: Zhao Qin and Francisco Martin-Martinez

A June 26, 2019 American Chemical Society (ACS) news release, which originated the news item, provides more detail and a video,

To make proteins, cellular structures called ribosomes add one of 20 different amino acids to a growing chain in combinations specified by the genetic blueprint. The properties of the amino acids and the complex shapes into which the resulting proteins fold determine how the molecule will work in the body. To better understand a protein’s architecture, and possibly design new ones with desired features, Markus Buehler and colleagues wanted to find a way to translate a protein’s amino acid sequence into music.

The researchers transposed the unique natural vibrational frequencies of each amino acid into sound frequencies that humans can hear. In this way, they generated a scale consisting of 20 unique tones. Unlike musical notes, however, each amino acid tone consisted of the overlay of many different frequencies –– similar to a chord. Buehler and colleagues then translated several proteins into audio compositions, with the duration of each tone specified by the different 3D structures that make up the molecule. Finally, the researchers used artificial intelligence to recognize specific musical patterns that corresponded to certain protein architectures. The computer then generated scores and translated them into new-to-nature proteins. In addition to being a tool for protein design and for investigating disease mutations, the method could be helpful for explaining protein structure to broad audiences, the researchers say. They even developed an Android app [Amino Acid Synthesizer] to allow people to create their own bio-based musical compositions.

Here’s the ACS video,

A June 26, 2019 MIT news release (also on EurekAlert) provides some specifics and the MIT news release includes two embedded audio files,

Want to create a brand new type of protein that might have useful properties? No problem. Just hum a few bars.

In a surprising marriage of science and art, researchers at MIT have developed a system for converting the molecular structures of proteins, the basic building blocks of all living beings, into audible sound that resembles musical passages. Then, reversing the process, they can introduce some variations into the music and convert it back into new proteins never before seen in nature.

Although it’s not quite as simple as humming a new protein into existence, the new system comes close. It provides a systematic way of translating a protein’s sequence of amino acids into a musical sequence, using the physical properties of the molecules to determine the sounds. Although the sounds are transposed in order to bring them within the audible range for humans, the tones and their relationships are based on the actual vibrational frequencies of each amino acid molecule itself, computed using theories from quantum chemistry.

The system was developed by Markus Buehler, the McAfee Professor of Engineering and head of the Department of Civil and Environmental Engineering at MIT, along with postdoc Chi Hua Yu and two others. As described in the journal ACS Nano, the system translates the 20 types of amino acids, the building blocks that join together in chains to form all proteins, into a 20-tone scale. Any protein’s long sequence of amino acids then becomes a sequence of notes.

While such a scale sounds unfamiliar to people accustomed to Western musical traditions, listeners can readily recognize the relationships and differences after familiarizing themselves with the sounds. Buehler says that after listening to the resulting melodies, he is now able to distinguish certain amino acid sequences that correspond to proteins with specific structural functions. “That’s a beta sheet,” he might say, or “that’s an alpha helix.”

Learning the language of proteins

The whole concept, Buehler explains, is to get a better handle on understanding proteins and their vast array of variations. Proteins make up the structural material of skin, bone, and muscle, but are also enzymes, signaling chemicals, molecular switches, and a host of other functional materials that make up the machinery of all living things. But their structures, including the way they fold themselves into the shapes that often determine their functions, are exceedingly complicated. “They have their own language, and we don’t know how it works,” he says. “We don’t know what makes a silk protein a silk protein or what patterns reflect the functions found in an enzyme. We don’t know the code.”

By translating that language into a different form that humans are particularly well-attuned to, and that allows different aspects of the information to be encoded in different dimensions — pitch, volume, and duration — Buehler and his team hope to glean new insights into the relationships and differences between different families of proteins and their variations, and use this as a way of exploring the many possible tweaks and modifications of their structure and function. As with music, the structure of proteins is hierarchical, with different levels of structure at different scales of length or time.

The team then used an artificial intelligence system to study the catalog of melodies produced by a wide variety of different proteins. They had the AI system introduce slight changes in the musical sequence or create completely new sequences, and then translated the sounds back into proteins that correspond to the modified or newly designed versions. With this process they were able to create variations of existing proteins — for example of one found in spider silk, one of nature’s strongest materials — thus making new proteins unlike any produced by evolution.

Although the researchers themselves may not know the underlying rules, “the AI has learned the language of how proteins are designed,” and it can encode it to create variations of existing versions, or completely new protein designs, Buehler says. Given that there are “trillions and trillions” of potential combinations, he says, when it comes to creating new proteins “you wouldn’t be able to do it from scratch, but that’s what the AI can do.”

“Composing” new proteins

By using such a system, he says training the AI system with a set of data for a particular class of proteins might take a few days, but it can then produce a design for a new variant within microseconds. “No other method comes close,” he says. “The shortcoming is the model doesn’t tell us what’s really going on inside. We just know it works.

This way of encoding structure into music does reflect a deeper reality. “When you look at a molecule in a textbook, it’s static,” Buehler says. “But it’s not static at all. It’s moving and vibrating. Every bit of matter is a set of vibrations. And we can use this concept as a way of describing matter.”

The method does not yet allow for any kind of directed modifications — any changes in properties such as mechanical strength, elasticity, or chemical reactivity will be essentially random. “You still need to do the experiment,” he says. When a new protein variant is produced, “there’s no way to predict what it will do.”

The team also created musical compositions developed from the sounds of amino acids, which define this new 20-tone musical scale. The art pieces they constructed consist entirely of the sounds generated from amino acids. “There are no synthetic or natural instruments used, showing how this new source of sounds can be utilized as a creative platform,” Buehler says. Musical motifs derived from both naturally existing proteins and AI-generated proteins are used throughout the examples, and all the sounds, including some that resemble bass or snare drums, are also generated from the sounds of amino acids.

The researchers have created a free Android smartphone app, called Amino Acid Synthesizer, to play the sounds of amino acids and record protein sequences as musical compositions.

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

A Self-Consistent Sonification Method to Translate Amino Acid Sequences into Musical Compositions and Application in Protein Design Using Artificial Intelligence by Chi-Hua Yu, Zhao Qin, Francisco J. Martin-Martinez, Markus J. Buehler. ACS Nano 2019 XXXXXXXXXX-XXX DOI: https://doi.org/10.1021/acsnano.9b02180 Publication Date:June 26, 2019 Copyright © 2019 American Chemical Society

This paper is behind a paywall.

ETA October 23, 2019 1000 hours: Ooops! I almost forgot the link to the Aminot Acid Synthesizer.

Automated science writing?

It seems that automated science writing is not ready—yet. Still, an April 18, 2019 news item on ScienceDaily suggests that progress is being made,

The work of a science writer, including this one, includes reading journal papers filled with specialized technical terminology, and figuring out how to explain their contents in language that readers without a scientific background can understand.

Now, a team of scientists at MIT [Massachusetts Institute of Technology] and elsewhere has developed a neural network, a form of artificial intelligence (AI), that can do much the same thing, at least to a limited extent: It can read scientific papers and render a plain-English summary in a sentence or two.

An April 17, 2019 MIT news release, which originated the news item, delves into the research and its implications,

Even in this limited form, such a neural network could be useful for helping editors, writers, and scientists [emphasis mine] scan a large number of papers to get a preliminary sense of what they’re about. But the approach the team developed could also find applications in a variety of other areas besides language processing, including machine translation and speech recognition.

The work is described in the journal Transactions of the Association for Computational Linguistics, in a paper by Rumen Dangovski and Li Jing, both MIT graduate students; Marin Soljačić, a professor of physics at MIT; Preslav Nakov, a principal scientist at the Qatar Computing Research Institute, HBKU; and Mićo Tatalović, a former Knight Science Journalism fellow at MIT and a former editor at New Scientist magazine.

From AI for physics to natural language

The work came about as a result of an unrelated project, which involved developing new artificial intelligence approaches based on neural networks, aimed at tackling certain thorny problems in physics. However, the researchers soon realized that the same approach could be used to address other difficult computational problems, including natural language processing, in ways that might outperform existing neural network systems.

“We have been doing various kinds of work in AI for a few years now,” Soljačić says. “We use AI to help with our research, basically to do physics better. And as we got to be  more familiar with AI, we would notice that every once in a while there is an opportunity to add to the field of AI because of something that we know from physics — a certain mathematical construct or a certain law in physics. We noticed that hey, if we use that, it could actually help with this or that particular AI algorithm.”

This approach could be useful in a variety of specific kinds of tasks, he says, but not all. “We can’t say this is useful for all of AI, but there are instances where we can use an insight from physics to improve on a given AI algorithm.”

Neural networks in general are an attempt to mimic the way humans learn certain new things: The computer examines many different examples and “learns” what the key underlying patterns are. Such systems are widely used for pattern recognition, such as learning to identify objects depicted in photos.

But neural networks in general have difficulty correlating information from a long string of data, such as is required in interpreting a research paper. Various tricks have been used to improve this capability, including techniques known as long short-term memory (LSTM) and gated recurrent units (GRU), but these still fall well short of what’s needed for real natural-language processing, the researchers say.

The team came up with an alternative system, which instead of being based on the multiplication of matrices, as most conventional neural networks are, is based on vectors rotating in a multidimensional space. The key concept is something they call a rotational unit of memory (RUM).

Essentially, the system represents each word in the text by a vector in multidimensional space — a line of a certain length pointing in a particular direction. Each subsequent word swings this vector in some direction, represented in a theoretical space that can ultimately have thousands of dimensions. At the end of the process, the final vector or set of vectors is translated back into its corresponding string of words.

“RUM helps neural networks to do two things very well,” Nakov says. “It helps them to remember better, and it enables them to recall information more accurately.”

After developing the RUM system to help with certain tough physics problems such as the behavior of light in complex engineered materials, “we realized one of the places where we thought this approach could be useful would be natural language processing,” says Soljačić,  recalling a conversation with Tatalović, who noted that such a tool would be useful for his work as an editor trying to decide which papers to write about. Tatalović was at the time exploring AI in science journalism as his Knight fellowship project.

“And so we tried a few natural language processing tasks on it,” Soljačić says. “One that we tried was summarizing articles, and that seems to be working quite well.”

The proof is in the reading

As an example, they fed the same research paper through a conventional LSTM-based neural network and through their RUM-based system. The resulting summaries were dramatically different.

The LSTM system yielded this highly repetitive and fairly technical summary: “Baylisascariasis,” kills mice, has endangered the allegheny woodrat and has caused disease like blindness or severe consequences. This infection, termed “baylisascariasis,” kills mice, has endangered the allegheny woodrat and has caused disease like blindness or severe consequences. This infection, termed “baylisascariasis,” kills mice, has endangered the allegheny woodrat.

Based on the same paper, the RUM system produced a much more readable summary, and one that did not include the needless repetition of phrases: Urban raccoons may infect people more than previously assumed. 7 percent of surveyed individuals tested positive for raccoon roundworm antibodies. Over 90 percent of raccoons in Santa Barbara play host to this parasite.

Already, the RUM-based system has been expanded so it can “read” through entire research papers, not just the abstracts, to produce a summary of their contents. The researchers have even tried using the system on their own research paper describing these findings — the paper that this news story is attempting to summarize.

Here is the new neural network’s summary: Researchers have developed a new representation process on the rotational unit of RUM, a recurrent memory that can be used to solve a broad spectrum of the neural revolution in natural language processing.

It may not be elegant prose, but it does at least hit the key points of information.

Çağlar Gülçehre, a research scientist at the British AI company Deepmind Technologies, who was not involved in this work, says this research tackles an important problem in neural networks, having to do with relating pieces of information that are widely separated in time or space. “This problem has been a very fundamental issue in AI due to the necessity to do reasoning over long time-delays in sequence-prediction tasks,” he says. “Although I do not think this paper completely solves this problem, it shows promising results on the long-term dependency tasks such as question-answering, text summarization, and associative recall.”

Gülçehre adds, “Since the experiments conducted and model proposed in this paper are released as open-source on Github, as a result many researchers will be interested in trying it on their own tasks. … To be more specific, potentially the approach proposed in this paper can have very high impact on the fields of natural language processing and reinforcement learning, where the long-term dependencies are very crucial.”

The research received support from the Army Research Office, the National Science Foundation, the MIT-SenseTime Alliance on Artificial Intelligence, and the Semiconductor Research Corporation. The team also had help from the Science Daily website, whose articles were used in training some of the AI models in this research.

As usual, this ‘automated writing system’ is framed as a ‘helper’ not an usurper of anyone’s job. However, its potential for changing the nature of the work is there. About five years ago I featured another ‘automated writing’ story in a July 16, 2014 posting titled: ‘Writing and AI or is a robot writing this blog?’ You may have been reading ‘automated’ news stories for years. At the time, the focus was on sports and business.

Getting back to 2019 and science writing, here’s a link to and a citation for the paper,

Rotational Unit of Memory: A Novel Representation Unit for RNNs with Scalable Applications by Rumen Dangovski, Li Jing, Preslav Nakov, Mićo Tatalović and Marin Soljačić. Transactions of the Association for Computational Linguistics Volume 07, 2019 pp.121-138 DOI: https://doi.org/10.1162/tacl_a_00258 Posted Online 2019

© 2019 Association for Computational Linguistics. Distributed under a CC-BY 4.0 license.

This paper is open access.

Desalination waste as a useful resource?

For anyone not familiar with the concept, it’s possible to remove salt from water to make it potable (i.e., drinkable). With growing concerns about water shortages worldwide, turning the ocean into something drinkable is seen as a reasonable solution. One of the problems associated with the solution is waste. As you can see in this post, it’s a big problem.

Illustration depicts the potential of the suggested process. Brine, which could be obtained from the waste stream of reverse osmosis (RO) desalination plants, or from industrial plants or salt mining operations, can be processed to yield useful chemicals such as sodium hydroxide (NaOH) or hydrochloric acid (HCl). Credit: Illustration courtesy of the researchers [downloaded from https://www.sciencedaily.com/releases/2019/02/190213124439.htm]

A February 13, 2019 news item on ScienceDaily announced research from MIT (Massachusetts Institute of Technology) into research on desalination and waste,

The rapidly growing desalination industry produces water for drinking and for agriculture in the world’s arid coastal regions. But it leaves behind as a waste product a lot of highly concentrated brine, which is usually disposed of by dumping it back into the sea, a process that requires costly pumping systems and that must be managed carefully to prevent damage to marine ecosystems. Now, engineers at MIT say they have found a better way.

In a new study, they show that through a fairly simple process the waste material can be converted into useful chemicals — including ones that can make the desalination process itself more efficient

A February 13, 2019 MIT news release (also on EurekAlert), which originated the news item, describes the work in detail,

The approach can be used to produce sodium hydroxide, among other products. Otherwise known as caustic soda, sodium hydroxide can be used to pretreat seawater going into the desalination plant. This changes the acidity of the water, which helps to prevent fouling of the membranes used to filter out the salty water — a major cause of interruptions and failures in typical reverse osmosis desalination plants.

The concept is described today in the journal Nature Catalysis and in two other papers by MIT research scientist Amit Kumar, professor of mechanical engineering John. [sic] H. Lienhard V, and several others. Lienhard is the Jameel Professor of Water and Food and the director of the Abdul Latif Jameel Water and Food Systems Lab.

“The desalination industry itself uses quite a lot of it,” Kumar says of sodium hydroxide. “They’re buying it, spending money on it. So if you can make it in situ at the plant, that could be a big advantage.” The amount needed in the plants themselves is far less than the total that could be produced from the brine, so there is also potential for it to be a saleable product.

Sodium hydroxide is not the only product that can be made from the waste brine: Another important chemical used by desalination plants and many other industrial processes is hydrochloric acid, which can also easily be made on site from the waste brine using established chemical processing methods. The chemical can be used for cleaning parts of the desalination plant, but is also widely used in chemical production and as a source of hydrogen.

Currently, the world produces more than 100 billion liters (about 27 billion gallons) a day of water from desalination, which leaves a similar volume of concentrated brine. [emphases mine] Much of that is pumped back out to sea, and current regulations require costly outfall systems to ensure adequate dilution of the salts. Converting the brine can thus be both economically and ecologically beneficial, especially as desalination continues to grow rapidly around the world. “Environmentally safe discharge of brine is manageable with current technology, but it’s much better to recover resources from the brine and reduce the amount of brine released,” Lienhard says.

The method of converting the brine into useful products uses well-known and standard chemical processes, including initial nanofiltration to remove undesirable compounds, followed by one or more electrodialysis stages to produce the desired end product. While the processes being suggested are not new, the researchers have analyzed the potential for production of useful chemicals from brine and proposed a specific combination of products and chemical processes that could be turned into commercial operations to enhance the economic viability of the desalination process, while diminishing its environmental impact.

“This very concentrated brine has to be handled carefully to protect life in the ocean, and it’s a resource waste, and it costs energy to pump it back out to sea,” so turning it into a useful commodity is a win-win, Kumar says. And sodium hydroxide is such a ubiquitous chemical that “every lab at MIT has some,” he says, so finding markets for it should not be difficult.

The researchers have discussed the concept with companies that may be interested in the next step of building a prototype plant to help work out the real-world economics of the process. “One big challenge is cost — both electricity cost and equipment cost,” at this stage, Kumar says.

The team also continues to look at the possibility of extracting other, lower-concentration materials from the brine stream, he says, including various metals and other chemicals, which could make the brine processing an even more economically viable undertaking.

“One aspect that was mentioned … and strongly resonated with me was the proposal for such technologies to support more ‘localized’ or ‘decentralized’ production of these chemicals at the point-of-use,” says Jurg Keller, a professor of water management at the University of Queensland in Australia, who was not involved in this work. “This could have some major energy and cost benefits, since the up-concentration and transport of these chemicals often adds more cost and even higher energy demand than the actual production of these at the concentrations that are typically used.”

The research team also included MIT postdoc Katherine Phillips and undergraduate Janny Cai, and Uwe Schroder at the University of Braunschweig, in Germany. The work was supported by Cadagua, a subsidiary of Ferrovial, through the MIT Energy Initiative.

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

Direct electrosynthesis of sodium hydroxide and hydrochloric acid from brine streams by Amit Kumar, Katherine R. Phillips, Gregory P. Thiel, Uwe Schröder, & John H. Lienhard V. Nature Catalysis volume 2, pages106–113 (2019) DOI: https://doi.org/10.1038/s41929-018-0218-y Published 13 February 2019

This paper is behind a paywall.

Better performing solar cells with newly discovered property of pristine graphene

Light-harvesting devices—I like that better than solar cells or the like but I think that the term serves as a category rather than a name/label for a specific device. Enough musing. A December 17, 2018 news item on Nanowerk describes the latest about graphene and light-harvesting devices (Note: A link has been removed,

An international research team, co-led by a physicist at the University of California, Riverside, has discovered a new mechanism for ultra-efficient charge and energy flow in graphene, opening up opportunities for developing new types of light-harvesting devices.

The researchers fabricated pristine graphene — graphene with no impurities — into different geometric shapes, connecting narrow ribbons and crosses to wide open rectangular regions. They found that when light illuminated constricted areas, such as the region where a narrow ribbon connected two wide regions, they detected a large light-induced current, or photocurrent.

The finding that pristine graphene can very efficiently convert light into electricity could lead to the development of efficient and ultrafast photodetectors — and potentially more efficient solar panels.

A December 14, 2018 University of California at Riverside (UCR) news release by Iqbal Pittalwala (also on EurekAlert but published Dec. 17, 2018), which originated the news item,gives a brief description of graphene while adding context for this research,


Graphene, a 1-atom thick sheet of carbon atoms arranged in a hexagonal lattice, has many desirable material properties, such as high current-carrying capacity and thermal conductivity. In principle, graphene can absorb light at any frequency, making it ideal material for infrared and other types of photodetection, with wide applications in bio-sensing, imaging, and night vision.

In most solar energy harvesting devices, a photocurrent arises only in the presence of a junction between two dissimilar materials, such as “p-n” junctions, the boundary between two types of semiconductor materials. The electrical current is generated in the junction region and moves through the distinct regions of the two materials.

“But in graphene, everything changes,” said Nathaniel Gabor, an associate professor of physics at UCR, who co-led the research project. “We found that photocurrents may arise in pristine graphene under a special condition in which the entire sheet of graphene is completely free of excess electronic charge. Generating the photocurrent requires no special junctions and can instead be controlled, surprisingly, by simply cutting and shaping the graphene sheet into unusual configurations, from ladder-like linear arrays of contacts, to narrowly constricted rectangles, to tapered and terraced edges.”

Pristine graphene is completely charge neutral, meaning there is no excess electronic charge in the material. When wired into a device, however, an electronic charge can be introduced by applying a voltage to a nearby metal. This voltage can induce positive charge, negative charge, or perfectly balance negative and positive charges so the graphene sheet is perfectly charge neutral.

“The light-harvesting device we fabricated is only as thick as a single atom,” Gabor said. “We could use it to engineer devices that are semi-transparent. These could be embedded in unusual environments, such as windows, or they could be combined with other more conventional light-harvesting devices to harvest excess energy that is usually not absorbed. Depending on how the edges are cut to shape, the device can give extraordinarily different signals.”

The research team reports this first observation of an entirely new physical mechanism — a photocurrent generated in charge-neutral graphene with no need for p-n junctions — in Nature Nanotechnology today [Dec. 17, 2018].

Previous work by the Gabor lab showed a photocurrent in graphene results from highly excited “hot” charge carriers. When light hits graphene, high-energy electrons relax to form a population of many relatively cooler electrons, Gabor explained, which are subsequently collected as current. Even though graphene is not a semiconductor, this light-induced hot electron population can be used to generate very large currents.

“All of this behavior is due to graphene’s unique electronic structure,” he said. “In this ‘wonder material,’ light energy is efficiently converted into electronic energy, which can subsequently be transported within the material over remarkably long distances.”

He explained that, about a decade ago, pristine graphene was predicted to exhibit very unusual electronic behavior: electrons should behave like a liquid, allowing energy to be transferred through the electronic medium rather than by moving charges around physically.
“But despite this prediction, no photocurrent measurements had been done on pristine graphene devices — until now,” he said.

The new work on pristine graphene shows electronic energy travels great distances in the absence of excess electronic charge.

The research team has found evidence that the new mechanism results in a greatly enhanced photoresponse in the infrared regime with an ultrafast operation speed.
“We plan to further study this effect in a broad range of infrared and other frequencies, and measure its response speed,” said first author Qiong Ma, a postdoctoral associate in physics at the Massachusetts Institute of Technology, or MIT.

The researchers have provided an image illustrating their work,

Caption: Shining light on graphene: Although graphene has been studied vigorously for more than a decade, new measurements on high-performance graphene devices have revealed yet another unusual property. In ultra-clean graphene sheets, energy can flow over great distances, giving rise to an unprecedented response to light. Credit: Max Grossnickle and QMO Labs, UC Riverside.

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

Giant intrinsic photoresponse in pristine graphene by Qiong Ma, Chun Hung Lui, Justin C. W. Song, Yuxuan Lin, Jian Feng Kong, Yuan Cao, Thao H. Dinh, Nityan L. Nair, Wenjing Fang, Kenji Watanabe, Takashi Taniguchi, Su-Yang Xu, Jing Kong, Tomás Palacios, Nuh Gedik, Nathaniel M. Gabor, & Pablo Jarillo-Herrero. Nature Nanotechnology (2018) Published 17 December 2018 DOI: https://doi.org/10.1038/s41565-018-0323-8

This paper is behind a paywall.

Teaching molecular and synthetic biology in grades K-12

This* story actually started in 2018 with an August 1, 2018 Harvard University news release (h/t Aug. 1, 2018 news item on phys.org) by Leslie Brownell announcing molecular and synthetic biology educational kits that been tested in the classroom. (In 2019, a new kit was released but more about that later.)

As biologists have probed deeper into the molecular and genetic underpinnings of life, K-12 schools have struggled to provide a curriculum that reflects those advances. Hands-on learning is known to be more engaging and effective for teaching science to students, but even the most basic molecular and synthetic biology experiments require equipment far beyond an average classroom’s budget, and often involve the use of bacteria and other substances that can be difficult to manage outside a controlled lab setting.

Now, a collaboration between the Wyss Institute at Harvard University, MIT [Massachusetts Institute of Technology], and Northwestern University has developed BioBits, new educational biology kits that use freeze-dried cell-free (FD-CF) reactions to enable students to perform a range of simple, hands-on biological experiments. The BioBits kits introduce molecular and synthetic biology concepts without the need for specialized lab equipment, at a fraction of the cost of current standard experimental designs. The kits are described in two papers published in Science Advances [2018].

“The main motivation in developing these kits was to give students fun activities that allow them to actually see, smell, and touch the outcomes of the biological reactions they’re doing at the molecular level,” said Ally Huang, a co-first author on both papers who is an MIT graduate student in the lab of Wyss Founding Core Faculty member Jim Collins, Ph.D. “My hope is that they will inspire more kids to consider a career in STEM [science, technology, engineering, and math] and, more generally, give all students a basic understanding of how biology works, because they may one day have to make personal or policy decisions based on modern science.”

Synthetic and molecular biology frequently make use of the cellular machinery found in E. coli bacteria to produce a desired protein. But this system requires that the bacteria be kept alive and contained for an extended period of time, and involves several complicated preparation and processing steps. The FD-CF reactions pioneered in Collins’ lab for molecular manufacturing, when combined with innovations from the lab of Michael Jewett, Ph.D. at Northwestern University, offer a solution to this problem by removing bacteria from the equation altogether.

“You can think of it like opening the hood of a car and taking the engine out: we’ve taken the ‘engine’ that drives protein production out of a bacterial cell and given it the fuel it needs, including ribosomes and amino acids, to create proteins from DNA outside of the bacteria itself,” explained Jewett, who is the Charles Deering McCormick Professor of Teaching Excellence at Northwestern University’s McCormick School of Engineering and co-director of Northwestern’s Center for Synthetic Biology, and co-corresponding author of both papers. This collection of molecular machinery is then freeze-dried into pellets so that it becomes shelf-stable at room temperature. To initiate the transcription of DNA into RNA and the translation of that RNA into a protein, a student just needs to add the desired DNA and water to the freeze-dried pellets.

The researchers designed a range of molecular experiments that can be performed using this system, and coupled each of them to a signal that the students can easily detect with their sense of sight, smell, or touch. The first, called BioBits Bright, contains six different freeze-dried DNA templates that each encode a protein that fluoresces a different color when illuminated with blue light. To produce the proteins, students simply add these DNA templates and water to the FD-CF machinery and put the reactions in an inexpensive incubator (~$30) for several hours, and then view them with a blue light illuminator (~$15). The students can also design their own experiments to produce a desired collection of colors that they can then arrange into a visual image, a bit like using a Light Brite ©. “Challenging the students to build their own in vitro synthetic programs also allows educators to start to talk about how synthetic biologists might control biology to make important products, such as medicines or chemicals,” explained Jessica Stark, an NSF Graduate Research Fellow in the Jewett lab at Northwestern University who is co-first author on both papers.

An expansion of the BioBits Bright kit, called BioBits Explorer, includes experiments that engage the senses of smell and touch and allow students to probe their environment using designer synthetic biosensors. In the first experiment, the FD-CF reaction pellets contain a gene that drives the conversion of isoamyl alcohol to isoamyl acetate, a compound that produces a strong banana odor. In the second experiment, the FD-CF reactions contain a gene coding for the enzyme sortase, which recognizes and links specific segments of proteins in a liquid solution together to form a squishy, semi-solid hydrogel, which the students can touch and manipulate. The third module uses another Wyss technology, the toehold switch sensor, to identify DNA extracted from a banana or a kiwi. The sensors are hairpin-shaped RNA molecules designed such that when they bind to a “trigger” RNA, they spring open and reveal a genetic sequence that produces a fluorescent protein. When fruit DNA is added to the sensor-containing FD-CF pellets, only the sensors that are designed to open in the presence of each fruit’s RNA will produce the fluorescent protein.

The researchers tested their BioBits kits in the Chicago Public School system, and demonstrated that students and teachers were able to perform the experiments in the kits with the same success as trained synthetic biology researchers. In addition to refining the kits’ design so that they can one day provide them to classrooms around the world, the authors hope to create an open-source online database where teachers and students can share their results and ideas for ways to modify the kits to explore different biological questions.

“Synthetic biology is going to be one of the defining technologies of the century, and yet it has been challenging to teach the fundamental concepts of the field in K-12 classrooms given that such efforts often require expensive, complicated equipment,” said Collins, who is a co-corresponding author of both papers and also the Termeer Professor of Medical Engineering & Science at MIT. “We show that it is possible to use freeze-dried, cell-free extracts along with freeze-dried synthetic biology components to conduct innovative educational experiments in classrooms and other low-resource settings. The BioBits kits enable us to expose young kids, older kids, and even adults to the wonders of synthetic biology and, as a result, are poised to transform science education and society.

“All scientists are passionate about what they do, and we are frustrated by the difficulty our educational system has had in inciting a similar level of passion in young people. This BioBits project demonstrates the kind of out-of-the-box thinking and refusal to accept the status quo that we value and cultivate at the Wyss Institute, and we all hope it will stimulate young people to be intrigued by science,” said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School (HMS) and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at Harvard’s John A. Paulson School of Engineering and Applied Sciences (SEAS). “It’s exciting to see this project move forward and become available to biology classrooms worldwide and, hopefully some of these students will pursue a path in science because of their experience.”

Additional authors of the papers include Peter Nguyen, Ph.D., Nina Donghia, and Tom Ferrante from the Wyss Institute; Melissa Takahashi, Ph.D. and Aaron Dy from MIT; Karen Hsu and Rachel Dubner from Northwestern University; Keith Pardee, Ph.D., Assistant Professor at the University of Toronto; and a number of teachers and students in the Chicago school system including: Mary Anderson, Ada Kanapskyte, Quinn Mucha, Jessica Packett, Palak Patel, Richa Patel, Deema Qaq, Tyler Zondor, Julie Burke, Tom Martinez, Ashlee Miller-Berry, Aparna Puppala, Kara Reichert, Miriam Schmid, Lance Brand, Lander Hill, Jemima Chellaswamy, Nuhie Faheem, Suzanne Fetherling, Elissa Gong, Eddie Marie Gonzales, Teresa Granito, Jenna Koritsaris, Binh Nguyen, Sujud Ottman, Christina Palffy, Angela Patel, Sheila Skweres, Adriane Slaton, and TaRhonda Woods.

This research was supported by the Army Research Office, the National Science Foundation, the Air Force Research Laboratory Center of Excellence Grant, The Defense Threat Reduction Agency Grant, the David and Lucile Packard Foundation, the Camille Dreyfus Teacher-Scholar Program, the Wyss Institute at Harvard University, the Paul G. Allen Frontiers Group, The Air Force Office of Scientific Research, and the Natural Sciences and Engineering Council of Canada. [emphases mine]

Well, that list of funding agencies is quite interesting. The US Army and Air Force but not the Navy? As for what the Natural Sciences and Engineering Council of Canada is doing on that list, I can only imagine why.

This is what they were doing in 2018,

Now for the latest update, a May 7, 2019 news item on phys.org announces the BioBits Kits have been expanded,

How can high school students learn about a technology as complex and abstract as CRISPR? It’s simple: just add water.

A Northwestern University-led team has developed BioBits, a suite of hands-on educational kits that enable students to perform a range of biological experiments by adding water and simple reagents to freeze-dried cell-free reactions. The kits link complex biological concepts to visual, fluorescent readouts, so students know—after a few hours and with a single glance—the results of their experiments.

A May 7, 2019 Northwestern University news release (also on EurekAlert and received via email) by Amanda Morris, which originated the news item, provides more details,

After launching BioBits last summer, the researchers are now expanding the kit to include modules for CRISPR [clustered regularly interspaced short palindromic repeats] and antibiotic resistance. A small group of Chicago-area teachers and high school students just completed the first pilot study for these new modules, which include interactive experiments and supplementary materials exploring ethics and strategies.

“After we unveiled the first kits, we next wanted to tackle current topics that are important for society,” said Northwestern’s Michael Jewett, principal investigator of the study. “That led us to two areas: antibiotic resistance and gene editing.”

Called BioBits Health, the new kits and pilot study are detailed in a paper published today (May 7 [2019]) in the journal ACS Synthetic Biology.

Jewett is a professor of chemical and biological engineering in Northwestern’s McCormick School of Engineering and co-director of Northwestern’s Center for Synthetic Biology. Jessica Stark, a graduate student in Jewett’s laboratory, led the study.

Test in a tube

Instead of using live cells, the BioBits team removed the essential cellular machinery from inside the cells and freeze-dried them for shelf stability. Keeping cells alive and contained for an extended period of time involves several complicated, time-consuming preparation and processing steps as well as expensive equipment. Freeze-dried cell-free reactions bypass those complications and costs.

“These are essentially test-tube biological reactions,” said Stark, a National Science Foundation graduate research fellow. “We break the cells open and use their guts, which still contain all of the necessary biological machinery to carry out a reaction. We no longer need living cells to demonstrate biology.”

This method to harness biological systems without intact, living cells became possible over the last two decades thanks to multiple innovations, including many in cell-free synthetic biology by Jewett’s lab. Not only are these experiments doable in the classroom, they also only cost pennies compared to standard high-tech experimental designs.

“I’m hopeful that students get excited about engineering biology and want to learn more,” Jewett said.

Conquering CRISPR

One of the biggest scientific breakthroughs of the past decade, CRISPR (pronounced “crisper”) stands for Clustered Regularly Interspaced Short Palindromic Repeats. The powerful gene-editing technology uses enzymes to cut DNA in precise locations to turn off or edit targeted genes. It could be used to halt genetic diseases, develop new medicines, make food more nutritious and much more.

BioBits Health uses three components required for CRISPR: an enzyme called the Cas9 protein, a target DNA sequence encoding a fluorescent protein and an RNA molecule that targets the fluorescent protein gene. When students add all three components — and water — to the freeze-dried cell-free system, it creates a reaction that edits, or cuts, the DNA for the fluorescent protein. If the DNA is cut, the system does not glow. If the DNA is not cut, the fluorescent protein is made, and the system glows fluorescent.

“We have linked this abstract, really advanced biological concept to the presence or absence of a fluorescent protein,” Stark said. “It’s something students can see, something they can visually understand.”

The curriculum also includes activities that challenge students to consider the ethical questions and dilemmas surrounding the use of gene-editing technologies.

“There is a lot of excitement about being able to edit genomes with these technologies,” Jewett said. “BioBits Health calls attention to a lot of important questions — not only about how CRISPR technology works but about ethics that society should be thinking about. We hope that this promotes a conversation and dialogue about such technologies.”

Reducing resistance

Jewett and Stark are both troubled by a prediction that, by the year 2050, drug-resistant bacterial infections could outpace cancer as a leading cause of death. This motivated them to help educate the future generation of scientists about how antibiotic resistance emerges and inspire them to take actions that could help limit the emergence of resistant bacteria.
In this module, students run two sets of reactions to produce a glowing fluorescent protein — one set with an antibiotic resistance gene and one set without. Students then add antibiotics. If the experiment glows, the fluorescent protein has been made, and the reaction has become resistant to antibiotics. If the experiment does not glow, then the antibiotic has worked.

“Because we’re using cell-free systems rather than organisms, we can demonstrate drug resistance in a way that doesn’t create drug-resistant bacteria,” Stark explained. “We can demonstrate these concepts without the risks.”

A supporting curriculum piece challenges students to brainstorm and research strategies for slowing the rate of emerging antibiotic resistant strains.

Part of something cool

After BioBits was launched in summer 2018, 330 schools from around the globe requested prototype kits for their science labs. The research team, which includes members from Northwestern and MIT, has received encouraging feedback from teachers, students and parents.

“The students felt like scientists and doctors by touching and using the laboratory materials provided during the demo,” one teacher said. “Even the students who didn’t seem engaged were secretly paying attention and wanted to take their turn pipetting. They knew they were part of something really cool, so we were able to connect with them in a way that was new to them.”

“My favorite part was using the equipment,” a student said. “It was a fun activity that immerses you into what top scientists are currently doing.”

###

The study, “BioBits Health: Classroom activities exploring engineering, biology and human health with fluorescent readouts,” was supported by the Army Research Office (award number W911NF-16-1-0372), the National Science Foundation (grant numbers MCB-1413563 and MCB-1716766), the Air Force Research Laboratory Center of Excellence (grant number FA8650-15-2-5518), the Defense Threat Reduction Agency (grant number HDTRA1-15-10052/P00001), the Department of Energy (grant number DE-SC0018249), the Human Frontiers Science Program (grant number RGP0015/2017), the David and Lucile Packard Foundation, the Office of Energy Efficiency and Renewable Energy (grant number DE-EE008343) and the Camille Dreyfus Teacher-Scholar Program. [emphases mine]

This is an image you’ll find in the abstract for the 2019 paper,

[downloaded from https://pubs.acs.org/doi/10.1021/acssynbio.8b00381]

Here are links and citations for the 2018 papers and the 2019 paper,

BioBits™ Explorer: A modular synthetic biology education kit by Ally Huang, Peter Q. Nguyen, Jessica C. Stark, Melissa K. Takahashi, Nina Donghia, Tom Ferrante, Aaron J. Dy, Karen J. Hsu, Rachel S. Dubner, Keith Pardee, Michael C. Jewett, and James J. Collins. Science Advances 01 Aug 2018: Vol. 4, no. 8, eaat5105 DOI: 10.1126/sciadv.aat5105

BioBits™ Bright: A fluorescent synthetic biology education kit by Jessica C. Stark, Ally Huang, Peter Q. Nguyen, Rachel S. Dubner, Karen J. Hsu, Thomas C. Ferrante, Mary Anderson, Ada Kanapskyte, Quinn Mucha, Jessica S. Packett, Palak Patel, Richa Patel, Deema Qaq, Tyler Zondor, Julie Burke, Thomas Martinez, Ashlee Miller-Berry, Aparna Puppala, Kara Reichert, Miriam Schmid, Lance Brand, Lander R. Hill, Jemima F. Chellaswamy, Nuhie Faheem, Suzanne Fetherling, Elissa Gong, Eddie Marie Gonzalzles, Teresa Granito, Jenna Koritsaris, Binh Nguyen, Sujud Ottman, Christina Palffy, Angela Patel, Sheila Skweres, Adriane Slaton, TaRhonda Woods, Nina Donghia, Keith Pardee, James J. Collins, and Michael C. Jewett. Science Advances 01 Aug 2018: Vol. 4, no. 8, eaat5107 DOI: 10.1126/sciadv.aat5107

BioBits Health: Classroom Activities Exploring Engineering, Biology, and Human Health with Fluorescent Readouts by Jessica C. Stark, Ally Huang, Karen J. Hsu, Rachel S. Dubner, Jason Forbrook, Suzanne Marshalla, Faith Rodriguez, Mechelle Washington, Grant A. Rybnicky, Peter Q. Nguyen, Brenna Hasselbacher, Ramah Jabri, Rijha Kamran, Veronica Koralewski, Will Wightkin, Thomas Martinez, and Michael C. Jewett. ACS Synth. Biol., Article ASAP
DOI: 10.1021/acssynbio.8b00381 Publication Date (Web): March 29, 2019

Copyright © 2019 American Chemical Society

Both of the 2018 papers appear to be open access while the 2019 paper is behind a paywall.

Should you be interested in acquiring a BioBits kit, you can check out the BioBits website. As for ‘conguering’ CRISPR, do we really need to look at it that way? Maybe a more humble appraoch could work just as well or even better, eh?

*’is’ removed from sentence on May 9, 2019.

The wonder of movement in 3D

Shades of Eadweard Muybridge (English photographer who pioneered photographic motion studies)! A September 19, 2018 news item on ScienceDaily describes the latest efforts to ‘capture motion’,

Patriots quarterback Tom Brady has often credited his success to spending countless hours studying his opponent’s movements on film. This understanding of movement is necessary for all living species, whether it’s figuring out what angle to throw a ball at, or perceiving the motion of predators and prey. But simple videos can’t actually give us the full picture.

That’s because traditional videos and photos for studying motion are two-dimensional, and don’t show us the underlying 3-D structure of the person or subject of interest. Without the full geometry, we can’t inspect the small and subtle movements that help us move faster, or make sense of the precision needed to perfect our athletic form.

Recently, though, researchers from MIT’s [Massachusetts Institute of Technology] Computer Science and Artificial Intelligence Laboratory (CSAIL) have come up with a way to get a better handle on this understanding of complex motion.

There isn’t a single reference to Muybridge, still, this September 18, 2018 Massachusetts Institute of Technology news release (also on EurekAlert but published September 19, 2018), which originated the news item, delves further into the research,

The new system uses an algorithm that can take 2-D videos and turn them into 3-D printed “motion sculptures” that show how a human body moves through space. In addition to being an intriguing aesthetic visualization of shape and time, the team envisions that their “MoSculp” system could enable a much more detailed study of motion for professional athletes, dancers, or anyone who wants to improve their physical skills.

“Imagine you have a video of Roger Federer serving a ball in a tennis match, and a video of yourself learning tennis,” says PhD student Xiuming Zhang, lead author of a new paper about the system. “You could then build motion sculptures of both scenarios to compare them and more comprehensively study where you need to improve.”

Because motion sculptures are 3-D, users can use a computer interface to navigate around the structures and see them from different viewpoints, revealing motion-related information inaccessible from the original viewpoint.

Zhang wrote the paper alongside MIT professors William Freeman and Stefanie Mueller, PhD student Jiajun Wu, Google researchers Qiurui He and Tali Dekel, as well as U.C. Berkeley postdoc and former CSAIL PhD Andrew Owens.

How it works

Artists and scientists have long struggled to gain better insight into movement, limited by their own camera lens and what it could provide.

Previous work has mostly used so-called “stroboscopic” photography techniques, which look a lot like the images in a flip book stitched together. But since these photos only show snapshots of movement, you wouldn’t be able to see as much of the trajectory of a person’s arm when they’re hitting a golf ball, for example.

What’s more, these photographs also require laborious pre-shoot setup, such as using a clean background and specialized depth cameras and lighting equipment. All MoSculp needs is a video sequence.

Given an input video, the system first automatically detects 2-D key points on the subject’s body, such as the hip, knee, and ankle of a ballerina while she’s doing a complex dance sequence. Then, it takes the best possible poses from those points to be turned into 3-D “skeletons.”

After stitching these skeletons together, the system generates a motion sculpture that can be 3-D printed, showing the smooth, continuous path of movement traced out by the subject. Users can customize their figures to focus on different body parts, assign different materials to distinguish among parts, and even customize lighting.

In user studies, the researchers found that over 75 percent of subjects felt that MoSculp provided a more detailed visualization for studying motion than the standard photography techniques.

“Dance and highly-skilled athletic motions often seem like ‘moving sculptures’ but they only create fleeting and ephemeral shapes,” says Courtney Brigham, communications lead at Adobe. “This work shows how to take motions and turn them into real sculptures with objective visualizations of movement, providing a way for athletes to analyze their movements for training, requiring no more equipment than a mobile camera and some computing time.”

The system works best for larger movements, like throwing a ball or taking a sweeping leap during a dance sequence. It also works for situations that might obstruct or complicate movement, such as people wearing loose clothing or carrying objects.

Currently, the system only uses single-person scenarios, but the team soon hopes to expand to multiple people. This could open up the potential to study things like social disorders, interpersonal interactions, and team dynamics.

This work will be presented at the User Interface Software and Technology (UIST) symposium in Berlin, Germany in October 2018 and the team’s paper published as part of the proceedings.

As for anyone wondering about the Muybridge comment, here’s an image the MIT researchers have made available,

A new system uses an algorithm that can take 2-D videos and turn them into 3-D-printed “motion sculptures” that show how a human body moves through space. Image courtesy of MIT CSAIL

Contrast that MIT image with some of the images in this video capturing parts of a theatre production, Studies in Motion: The Hauntings of Eadweard Muybridge,

Getting back to MIT, here’s their MoSculp video,

There are some startling similarities, eh? I suppose there are only so many ways one can capture movement be it in studies of Eadweard Muybridge, a theatre production about his work, or an MIT video the latest in motion capture technology.

Manipulating light at the nanoscale with kiragami-inspired technique

At left, different patterns of slices through a thin metal foil, are made by a focused ion beam. These patterns cause the metal to fold up into predetermined shapes, which can be used for such purposes as modifying a beam of light. Courtesy of the researchers

Nanokiragami (or nano-kiragami) is a fully fledged field of research? That was news to me as was much else in a July 6, 2018 news item on ScienceDaily,

Nanokirigami has taken off as a field of research in the last few years; the approach is based on the ancient arts of origami (making 3-D shapes by folding paper) and kirigami (which allows cutting as well as folding) but applied to flat materials at the nanoscale, measured in billionths of a meter.

Now, researchers at MIT [Massachusetts Institute of Technology] and in China have for the first time applied this approach to the creation of nanodevices to manipulate light, potentially opening up new possibilities for research and, ultimately, the creation of new light-based communications, detection, or computational devices.

A July 6, 2018 MIT news release (also on EurekAlert), which originated the news item, adds detail,

The findings are described today [July 6, 2018] in the journal Science Advances, in a paper by MIT professor of mechanical engineering Nicholas X Fang and five others. Using methods based on standard microchip manufacturing technology, Fang and his team used a focused ion beam to make a precise pattern of slits in a metal foil just a few tens of nanometers thick. The process causes the foil to bend and twist itself into a complex three-dimensional shape capable of selectively filtering out light with a particular polarization.

Previous attempts to create functional kirigami devices have used more complicated fabrication methods that require a series of folding steps and have been primarily aimed at mechanical rather than optical functions, Fang says. The new nanodevices, by contrast, can be formed in a single folding step and could be used to perform a number of different optical functions.

For these initial proof-of-concept devices, the team produced a nanomechanical equivalent of specialized dichroic filters that can filter out circularly polarized light that is either “right-handed” or “left-handed.” To do so, they created a pattern just a few hundred nanometers across in the thin metal foil; the result resembles pinwheel blades, with a twist in one direction that selects the corresponding twist of light.

The twisting and bending of the foil happens because of stresses introduced by the same ion beam that slices through the metal. When using ion beams with low dosages, many vacancies are created, and some of the ions end up lodged in the crystal lattice of the metal, pushing the lattice out of shape and creating strong stresses that induce the bending.

“We cut the material with an ion beam instead of scissors, by writing the focused ion beam across this metal sheet with a prescribed pattern,” Fang says. “So you end up with this metal ribbon that is wrinkling up” in the precisely planned pattern.

“It’s a very nice connection of the two fields, mechanics and optics,” Fang says. The team used helical patterns to separate out the clockwise and counterclockwise polarized portions of a light beam, which may represent “a brand new direction” for nanokirigami research, he says.

The technique is straightforward enough that, with the equations the team developed, researchers should now be able to calculate backward from a desired set of optical characteristics and produce the needed pattern of slits and folds to produce just that effect, Fang says.

“It allows a prediction based on optical functionalities” to create patterns that achieve the desired result, he adds. “Previously, people were always trying to cut by intuition” to create kirigami patterns for a particular desired outcome.

The research is still at an early stage, Fang points out, so more research will be needed on possible applications. But these devices are orders of magnitude smaller than conventional counterparts that perform the same optical functions, so these advances could lead to more complex optical chips for sensing, computation, or communications systems or biomedical devices, the team says.

For example, Fang says, devices to measure glucose levels often use measurements of light polarity, because glucose molecules exist in both right- and left-handed forms which interact differently with light. “When you pass light through the solution, you can see the concentration of one version of the molecule, as opposed to the mixture of both,” Fang explains, and this method could allow for much smaller, more efficient detectors.

Circular polarization is also a method used to allow multiple laser beams to travel through a fiber-optic cable without interfering with each other. “People have been looking for such a system for laser optical communications systems” to separate the beams in devices called optical isolaters, Fang says. “We have shown that it’s possible to make them in nanometer sizes.”

The team also included MIT graduate student Huifeng Du; Zhiguang Liu, Jiafang Li (project supervisor), and Ling Lu at the Chinese Academy of Sciences in Beijing; and Zhi-Yuan Li at the South China University of Technology. The work was supported by the National Key R&D Program of China, the National Natural Science Foundation of China, and the U.S Air Force Office of Scientific Research.

The researchers have also provided some GIFs,

And,

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

Nano-kirigami with giant optical chirality by Zhiguang Liu, Huifeng Du, Jiafang Li, Ling Lu, Zhi-Yuan Li, and Nicholas X. Fang. Science Advances 06 Jul 2018: Vol. 4, no. 7, eaat4436 DOI: 10.1126/sciadv.aat4436

This paper is open access.

First CRISPR gene-edited babies? Ethics and the science story

Scientists, He Jiankui and Michael Deem, may have created the first human babies born after being subjected to CRISPR (clustered regularly interspaced short palindromic repeats) gene editing.  At this point, no one is entirely certain that these babies  as described actually exist since the information was made public in a rather unusual (for scientists) fashion.

The news broke on Sunday, November 25, 2018 through a number of media outlets none of which included journals associated with gene editing or high impact journals such as Cell, Nature, or Science.The news broke in MIT Technology Review and in Associated Press. Plus, this all happened just before the Second International Summit on Human Genome Editing (Nov. 27 – 29, 2018) in Hong Kong. He Jiankui was scheduled to speak today, Nov. 27, 2018.

Predictably, this news has caused quite a tizzy.

Breaking news

Antonio Regalado broke the news in a November 25, 2018  article for MIT [Massachusetts Institute of Technology] Technology Review (Note: Links have been removed),

According to Chinese medical documents posted online this month (here and here), a team at the Southern University of Science and Technology, in Shenzhen, has been recruiting couples in an effort to create the first gene-edited babies. They planned to eliminate a gene called CCR5 in hopes of rendering the offspring resistant to HIV, smallpox, and cholera.

The clinical trial documents describe a study in which CRISPR is employed to modify human embryos before they are transferred into women’s uteruses.

The scientist behind the effort, He Jiankui, did not reply to a list of questions about whether the undertaking had produced a live birth. Reached by telephone, he declined to comment.

However, data submitted as part of the trial listing shows that genetic tests have been carried out on fetuses as late as 24 weeks, or six months. It’s not known if those pregnancies were terminated, carried to term, or are ongoing.

Apparently He changed his mind because Marilynn Marchione in a November 26, 2018 article for the Associated Press confirms the news,

A Chinese researcher claims that he helped make the world’s first genetically edited babies — twin girls born this month whose DNA he said he altered with a powerful new tool capable of rewriting the very blueprint of life.

If true, it would be a profound leap of science and ethics.

A U.S. scientist [Dr. Michael Deem] said he took part in the work in China, but this kind of gene editing is banned in the United States because the DNA changes can pass to future generations and it risks harming other genes.

Many mainstream scientists think it’s too unsafe to try, and some denounced the Chinese report as human experimentation.

There is no independent confirmation of He’s claim, and it has not been published in a journal, where it would be vetted by other experts. He revealed it Monday [November 26, 2018] in Hong Kong to one of the organizers of an international conference on gene editing that is set to begin Tuesday [November 27, 2018], and earlier in exclusive interviews with The Associated Press.

“I feel a strong responsibility that it’s not just to make a first, but also make it an example,” He told the AP. “Society will decide what to do next” in terms of allowing or forbidding such science.

Some scientists were astounded to hear of the claim and strongly condemned it.

It’s “unconscionable … an experiment on human beings that is not morally or ethically defensible,” said Dr. Kiran Musunuru, a University of Pennsylvania gene editing expert and editor of a genetics journal.

“This is far too premature,” said Dr. Eric Topol, who heads the Scripps Research Translational Institute in California. “We’re dealing with the operating instructions of a human being. It’s a big deal.”

However, one famed geneticist, Harvard University’s George Church, defended attempting gene editing for HIV, which he called “a major and growing public health threat.”

“I think this is justifiable,” Church said of that goal.

h/t Cale Guthrie Weissman’s Nov. 26, 2018 article for Fast Company.

Diving into more detail

Ed Yong in a November 26, 2018 article for The Atlantic provides more details about the claims (Note: Links have been removed),

… “Two beautiful little Chinese girls, Lulu and Nana, came crying into the world as healthy as any other babies a few weeks ago,” He said in the first of five videos, posted yesterday {Nov. 25, 2018] to YouTube [link provided at the end of this section of the post]. “The girls are home now with their mom, Grace, and dad, Mark.” The claim has yet to be formally verified, but if true, it represents a landmark in the continuing ethical and scientific debate around gene editing.

Late last year, He reportedly enrolled seven couples in a clinical trial, and used their eggs and sperm to create embryos through in vitro fertilization. His team then used CRISPR to deactivate a single gene called CCR5 in the embryos, six of which they then implanted into mothers. CCR5 is a protein that the HIV virus uses to gain entry into human cells; by deactivating it, the team could theoretically reduce the risk of infection. Indeed, the fathers in all eight couples were HIV-positive.

Whether the experiment was successful or not, it’s intensely controversial. Scientists have already begun using CRISPR and other gene-editing technologies to alter human cells, in attempts to treat cancers, genetic disorders, and more. But in these cases, the affected cells stay within a person’s body. Editing an embryo [it’s often called, germline editing] is very different: It changes every cell in the body of the resulting person, including the sperm or eggs that would pass those changes to future generations. Such work is banned in many European countries, and prohibited in the United States. “I understand my work will be controversial, but I believe families need this technology and I’m willing to take the criticism for them,” He said.

“Was this a reasonable thing to do? I would say emphatically no,” says Paula Cannon of the University of Southern California. She and others have worked on gene editing, and particularly on trials that knock out CCR5 as a way to treat HIV. But those were attempts to treat people who were definitively sick and had run out of other options. That wasn’t the case with Nana and Lulu.

“The idea that being born HIV-susceptible, which is what the vast majority of humans are, is somehow a disease state that requires the extraordinary intervention of gene editing blows my mind,” says Cannon. “I feel like he’s appropriating this potentially valuable therapy as a shortcut to doing something in the sphere of gene editing. He’s either very naive or very cynical.”

“I want someone to make sure that it has happened,” says Hank Greely, an ethicist at Stanford University. If it hasn’t, that “would be a pretty bald-faced fraud,” but such deceptions have happened in the past. “If it is true, I’m disappointed. It’s reckless on safety grounds, and imprudent and stupid on social grounds.” He notes that a landmark summit in 2015 (which included Chinese researchers) and a subsequent major report from the National Academies of Science, Engineering, and Medicine both argued that “public participation should precede any heritable germ-line editing.” That is: Society needs to work out how it feels about making gene-edited babies before any babies are edited. Absent that consensus, He’s work is “waving a red flag in front of a bull,” says Greely. “It provokes not just the regular bio-Luddites, but also reasonable people who just wanted to talk it out.”

Societally, the creation of CRISPR-edited babies is a binary moment—a Rubicon that has been crossed. But scientifically, the devil is in the details, and most of those are still unknown.

CRISPR is still inefficient. [emphasis mine] The Chinese teams who first used it to edit human embryos only did so successfully in a small proportion of cases, and even then, they found worrying levels of “off-target mutations,” where they had erroneously cut parts of the genome outside their targeted gene. He, in his video, claimed that his team had thoroughly sequenced Nana and Lulu’s genomes and found no changes in genes other than CCR5.

That claim is impossible to verify in the absence of a peer-reviewed paper, or even published data of any kind. “The paper is where we see whether the CCR5 gene was properly edited, what effect it had at the cellular level, and whether [there were] any off-target effects,” said Eric Topol of the Scripps Research Institute. “It’s not just ‘it worked’ as a binary declaration.”

In the video, He said that using CRISPR for human enhancement, such as enhancing IQ or selecting eye color, “should be banned.” Speaking about Nana and Lulu’s parents, he said that they “don’t want a designer baby, just a child who won’t suffer from a disease that medicine can now prevent.”

But his rationale is questionable. Huang [Junjiu Huang of Sun Yat-sen University ], the first Chinese researcher to use CRISPR on human embryos, targeted the faulty gene behind an inherited disease called beta thalassemia. Mitalipov, likewise, tried to edit a gene called MYBPC3, whose faulty versions cause another inherited disease called hypertrophic cardiomyopathy (HCM). Such uses are still controversial, but they rank among the more acceptable applications for embryonic gene editing as ways of treating inherited disorders for which treatments are either difficult or nonexistent.

In contrast, He’s team disableda normal gene in an attempt to reduce the risk of a disease that neither child had—and one that can be controlled. There are already ways of preventing fathers from passing HIV to their children. There are antiviral drugs that prevent infections. There’s safe-sex education. “This is not a plague for which we have no tools,” says Cannon.

As Marilynn Marchione of the AP reports, early tests suggest that He’s editing was incomplete [emphasis mine], and at least one of the twins is a mosaic, where some cells have silenced copies of CCR5 and others do not. If that’s true, it’s unlikely that they would be significantly protected from HIV. And in any case, deactivating CCR5 doesn’t confer complete immunity, because some HIV strains can still enter cells via a different protein called CXCR4.

Nana and Lulu might have other vulnerabilities. …

It is also unclear if the participants in He’s trial were fully aware of what they were signing up for. [emphasis mine] The team’s informed-consent document describes their work as an “AIDS vaccine development project,” and while it describes CRISPR gene editing, it does so in heavily technical language. It doesn’t mention any of the risks of disabling CCR5, and while it does note the possibility of off-target effects, it also says that the “project team is not responsible for the risk.”

He owns two genetics companies, and his collaborator, Michael Deem of Rice University,  [emphasis mine] holds a small stake in, and sits on the advisory board of, both of them. The AP’s Marchione reports, “Both men are physics experts with no experience running human clinical trials.” [emphasis mine]

Yong’s article is well worth reading in its entirety. As for YouTube, here’s The He Lab’s webpage with relevant videos.

Reactions

Gina Kolata, Sui-Lee Wee, and Pam Belluck writing in a Nov. 26, 2018 article for the New York Times chronicle some of the response to He’s announcement,

It is highly unusual for a scientist to announce a groundbreaking development without at least providing data that academic peers can review. Dr. He said he had gotten permission to do the work from the ethics board of the hospital Shenzhen Harmonicare, but the hospital, in interviews with Chinese media, denied being involved. Cheng Zhen, the general manager of Shenzhen Harmonicare, has asked the police to investigate what they suspect are “fraudulent ethical review materials,” according to the Beijing News.

The university that Dr. He is attached to, the Southern University of Science and Technology, said Dr. He has been on no-pay leave since February and that the school of biology believed that his project “is a serious violation of academic ethics and academic norms,” according to the state-run Beijing News.

In a statement late on Monday, China’s national health commission said it has asked the health commission in southern Guangdong province to investigate Mr. He’s claims.

“I think that’s completely insane,” said Shoukhrat Mitalipov, director of the Center for Embryonic Cell and Gene Therapy at Oregon Health and Science University. Dr. Mitalipov broke new ground last year by using gene editing to successfully remove a dangerous mutation from human embryos in a laboratory dish. [I wrote a three-part series about CRISPR, which included what was then the latest US news, Mitalipov’s announcement, along with a roundup of previous work in China. Links are at the end of this section.’

Dr. Mitalipov said that unlike his own work, which focuses on editing out mutations that cause serious diseases that cannot be prevented any other way, Dr. He did not do anything medically necessary. There are other ways to prevent H.I.V. infection in newborns.

Just three months ago, at a conference in late August on genome engineering at Cold Spring Harbor Laboratory in New York, Dr. He presented work on editing the CCR₅ gene in the embryos of nine couples.

At the conference, whose organizers included Jennifer Doudna, one of the inventors of Crispr technology, Dr. He gave a careful talk about something that fellow attendees considered squarely within the realm of ethically approved research. But he did not mention that some of those embryos had been implanted in a woman and could result in genetically engineered babies.

“What we now know is that as he was talking, there was a woman in China carrying twins,” said Fyodor Urnov, deputy director of the Altius Institute for Biomedical Sciences and a visiting researcher at the Innovative Genomics Institute at the University of California. “He had the opportunity to say ‘Oh and by the way, I’m just going to come out and say it, people, there’s a woman carrying twins.’”

“I would never play poker against Dr. He,” Dr. Urnov quipped.

Richard Hynes, a cancer researcher at the Massachusetts Institute of Technology, who co-led an advisory group on human gene editing for the National Academy of Sciences and the National Academy of Medicine, said that group and a similar organization in Britain had determined that if human genes were to be edited, the procedure should only be done to address “serious unmet needs in medical treatment, it had to be well monitored, it had to be well followed up, full consent has to be in place.”

It is not clear why altering genes to make people resistant to H.I.V. is “a serious unmet need.” Men with H.I.V. do not infect embryos. …

Dr. He got his Ph.D., from Rice University, in physics and his postdoctoral training, at Stanford, was with Stephen Quake, a professor of bioengineering and applied physics who works on sequencing DNA, not editing it.

Experts said that using Crispr would actually be quite easy for someone like Dr. He.

After coming to Shenzhen in 2012, Dr. He, at age 28, established a DNA sequencing company, Direct Genomics, and listed Dr. Quake on its advisory board. But, in a telephone interview on Monday, Dr. Quake said he was never associated with the company.

Deem, the US scientist who worked in China with He is currently being investigated (from a Nov. 26, 2018 article by Andrew Joseph in STAT),

Rice University said Monday that it had opened a “full investigation” into the involvement of one of its faculty members in a study that purportedly resulted in the creation of the world’s first babies born with edited DNA.

Michael Deem, a bioengineering professor at Rice, told the Associated Press in a story published Sunday that he helped work on the research in China.

Deem told the AP that he was in China when participants in the study consented to join the research. Deem also said that he had “a small stake” in and is on the scientific advisory boards of He’s two companies.

Megan Molteni in a Nov. 27, 2018 article for Wired admits she and her colleagues at the magazine may have dismissed CRISPR concerns about designer babies prematurely while shedding more light on this  latest development (Note: Links have been removed),

We said “don’t freak out,” when scientists first used Crispr to edit DNA in non-viable human embryos. When they tried it in embryos that could theoretically produce babies, we said “don’t panic.” Many years and years of boring bench science remain before anyone could even think about putting it near a woman’s uterus. Well, we might have been wrong. Permission to push the panic button granted.

Late Sunday night, a Chinese researcher stunned the world by claiming to have created the first human babies, a set of twins, with Crispr-edited DNA….

What’s perhaps most strange is not that He ignored global recommendations on conducting responsible Crispr research in humans. He also ignored his own advice to the world—guidelines that were published within hours of his transgression becoming public.

On Monday, He and his colleagues at Southern University of Science and Technology, in Shenzhen, published a set of draft ethical principles “to frame, guide, and restrict clinical applications that communities around the world can share and localize based on religious beliefs, culture, and public-health challenges.” Those principles included transparency and only performing the procedure when the risks are outweighed by serious medical need.

The piece appeared in the The Crispr Journal, a young publication dedicated to Crispr research, commentary, and debate. Rodolphe Barrangou, the journal’s editor in chief, where the peer-reviewed perspective appeared, says that the article was one of two that it had published recently addressing the ethical concerns of human germline editing, the other by a bioethicist at the University of North Carolina. Both papers’ authors had requested that their writing come out ahead of a major gene editing summit taking place this week in Hong Kong. When half-rumors of He’s covert work reached Barrangou over the weekend, his team discussed pulling the paper, but ultimately decided that there was nothing too solid to discredit it, based on the information available at the time.

Now Barrangou and his team are rethinking that decision. For one thing, He did not disclose any conflicts of interest, which is standard practice among respectable journals. It’s since become clear that not only is He at the helm of several genetics companies in China, He was actively pursuing controversial human research long before writing up a scientific and moral code to guide it.“We’re currently assessing whether the omission was a matter of ill-management or ill-intent,” says Barrangou, who added that the journal is now conducting an audit to see if a retraction might be warranted. …

“There are all sorts of questions these issues raise, but the most fundamental is the risk-benefit ratio for the babies who are going to be born,” says Hank Greely, an ethicist at Stanford University. “And the risk-benefit ratio on this stinks. Any institutional review board that approved it should be disbanded if not jailed.”

Reporting by Stat indicates that He may have just gotten in over his head and tried to cram a self-guided ethics education into a few short months. The young scientist—records indicate He is just 34—has a background in biophysics, with stints studying in the US at Rice University and in bioengineer Stephen Quake’s lab at Stanford. His resume doesn’t read like someone steeped deeply in the nuances and ethics of human research. Barrangou says that came across in the many rounds of edits He’s framework went through.

… China’s central government in Beijing has yet to come down one way or another. Condemnation would make He a rogue and a scientific outcast. Anything else opens the door for a Crispr IVF cottage industry to emerge in China and potentially elsewhere. “It’s hard to imagine this was the only group in the world doing this,” says Paul Knoepfler, a stem cell researcher at UC Davis who wrote a book on the future of designer babies called GMO Sapiens. “Some might say this broke the ice. Will others forge ahead and go public with their results or stop what they’re doing and see how this plays out?”

Here’s some of the very latest information with the researcher attempting to explain himself.

What does He have to say?

After He’s appearance at the Second International Summit on Human Genome Editing today, Nov. 27, 2018, David Cyranoski produced this article for Nature,

He Jiankui, the Chinese scientist who claims to have helped produce the first people born with edited genomes — twin girls — appeared today at a gene-editing summit in Hong Kong to explain his experiment. He gave his talk amid threats of legal action and mounting questions, from the scientific community and beyond, about the ethics of his work and the way in which he released the results.

He had never before presented his work publicly outside of a handful of videos he posted on YouTube. Scientists welcomed the fact that he appeared at all — but his talk left many hungry for more answers, and still not completely certain that He has achieved what he claims.

“There’s no reason not to believe him,” says Robin Lovell-Badge, a developmental biologist at the Francis Crick Institute in London. “I’m just not completely convinced.”

Lovell-Badge, like others at the conference, says that an independent body should confirm the test results by performing an in-depth comparison of the parents’ and childrens’ genes.

Many scientists faulted He for a lack of transparency and the seemingly cavalier nature in which he embarked on such a landmark, and potentially risky, project.

“I’m happy he came but I was really horrified and stunned when he described the process he used,” says Jennifer Doudna, a biochemist at the University of California, Berkeley and a pioneer of the CRISPR/Cas-9 gene-editing technique that He used. “It was so inappropriate on so many levels.”

He seemed shaky approaching the stage and nervous during the talk. “I think he was scared,” says Matthew Porteus, who researches genome-editing at Stanford University in California and co-hosted a question-and-answer session with He after his presentation. Porteus attributes this either to the legal pressures that He faces or the mounting criticism from the scientists and media he was about to address.

He’s talk leaves a host of other questions unanswered, including whether the prospective parents were properly informed of the risks; why He selected CCR5 when there are other, proven ways to prevent HIV; why he chose to do the experiment with couples in which the fathers have HIV, rather than mothers who have a higher chance of passing the virus on to their children; and whether the risks of knocking out CCR5 — a gene normally present in people, which could have necessary but still unknown functions — outweighed the benefits in this case.

In the discussion following He’s talk, one scientist asked why He proceeded with the experiments despite the clear consensus among scientists worldwide that such research shouldn’t be done. He didn’t answer the question.

He’s attempts to justify his actions mainly fell flat. In response to questions about why the science community had not been informed of the experiments before the first women were impregnated, he cited presentations that he gave last year at meetings at the University of California, Berkeley, and at the Cold Spring Harbor Laboratory in New York. But Doudna, who organized the Berkeley meeting, says He did not present anything that showed he was ready to experiment in people. She called his defence “disingenuous at best”.

He also said he discussed the human experiment with unnamed scientists in the United States. But Porteus says that’s not enough for such an extraordinary experiment: “You need feedback not from your two closest friends but from the whole community.” …

Pressure was mounting on He ahead of the presentation. On 27 November, the Chinese national health commission ordered the Guangdong health commission, in the province where He’s university is located, to investigate.

On the same day, the Chinese Academy of Sciences issued a statement condemning his work, and the Genetics Society of China and the Chinese Society for Stem Cell Research jointly issued a statement saying the experiment “violates internationally accepted ethical principles regulating human experimentation and human rights law”.

The hospital cited in China’s clinical-trial registry as the that gave ethical approval for He’s work posted a press release on 27 November saying it did not give any approval. It questioned the signatures on the approval form and said that the hospital’s medical-ethics committee never held a meeting related to He’s research. The hospital, which itself is under investigation by the Shenzhen health authorities following He’s revelations, wrote: “The Company does not condone the means of the Claimed Project, and has reservations as to the accuracy, reliability and truthfulness of its contents and results.”

He has not yet responded to requests for comment on these statements and investigations, nor on why the hospital was listed in the registry and the claim of apparent forged signatures.

Alice Park’s Nov. 26, 2018 article for Time magazine includes an embedded video of He’s Nov. 27, 2018 presentation at the summit meeting.

What about the politics?

Mara Hvistendahl’s Nov. 27, 2018 article about this research for Slate.com poses some geopolitical questions (Note: Links have been removed),

The informed consent agreement for He Jiankui’s experiment describes it as an “AIDS vaccine development project” and used highly technical language to describe the procedure that patients would undergo. If the reality for some Chinese patients is that such agreements are glossed over, densely written, or never read, the reality for some researchers working in the country is that the appeal of cutting-edge trials is too great to resist. It is not just Chinese scientists who can be blinded by the lure of quick breakthroughs. Several of the most notable breaches of informed consent on the mainland have involved Western researchers or co-authors. … When people say that the usual rules don’t apply in China, they are really referring to authoritarian science, not some alternative communitarian ethics.

For the many scientists in China who adhere to recognized international standards, the incident comes as a disgrace. He Jiankui now faces an ethics investigation from provincial health authorities, and his institution, Southern University of Science and Technology, was quick to issue a statement noting that He was on unpaid leave. …

It would seem that US [and from elsewhere]* scientists wanting to avoid pesky ethics requirements in the US have found that going to China could be the answer to their problems. I gather it’s not just big business that prefers deregulated environments.

Guillaume Levrier’s  (he’ studying for a PhD at the Universté Sorbonne Paris Cité) November 16, 2018 essay for The Conversation sheds some light on political will and its impact on science (Note: Links have been removed),

… China has entered a “genome editing” race among great scientific nations and its progress didn’t come out of nowhere. China has invested heavily in the natural-sciences sector over the past 20 years. The Ninth Five-Year Plan (1996-2001) mentioned the crucial importance of biotechnologies. The current Thirteenth Five-Year Plan is even more explicit. It contains a section dedicated to “developing efficient and advanced biotechnologies” and lists key sectors such as “genome-editing technologies” intended to “put China at the bleeding edge of biotechnology innovation and become the leader in the international competition in this sector”.

Chinese embryo research is regulated by a legal framework, the “technical norms on human-assisted reproductive technologies”, published by the Science and Health Ministries. The guidelines theoretically forbid using sperm or eggs whose genome have been manipulated for procreative purposes. However, it’s hard to know how much value is actually placed on this rule in practice, especially in China’s intricate institutional and political context.

In theory, three major actors have authority on biomedical research in China: the Science and Technology Ministry, the Health Ministry, and the Chinese Food and Drug Administration. In reality, other agents also play a significant role. Local governments interpret and enforce the ministries’ “recommendations”, and their own interpretations can lead to significant variations in what researchers can and cannot do on the ground. The Chinese National Academy of Medicine is also a powerful institution that has its own network of hospitals, universities and laboratories.

Another prime actor is involved: the health section of the People’s Liberation Army (PLA), which has its own biomedical faculties, hospitals and research labs. The PLA makes its own interpretations of the recommendations and has proven its ability to work with the private sector on gene editing projects. …

One other thing from Levrier’s essay,

… And the media timing is just a bit too perfect, …

Do read the essay; there’s a twist at the end.

Final thoughts and some links

If I read this material rightly, there are suspicions there may be more of this work being done in China and elsewhere. In short, we likely don’t have the whole story.

As for the ethical issues, this is a discussion among experts only, so far. The great unwashed (thee and me) are being left at the wayside. Sure, we’ll be invited to public consultations, one day,  after the big decisions have been made.

Anyone who’s read up on the history of science will tell you this kind of breach is very common at the beginning. Richard Holmes’  2008 book, ‘The Age of Wonder: How the Romantic Generation Discovered the Beauty and Terror of Science’ recounts stories of early scientists (European science) who did crazy things. Some died, some shortened their life spans; and, some irreversibly damaged their health.  They also experimented on other people. Informed consent had not yet been dreamed up.

In fact, I remember reading somewhere that the largest human clinical trial in history was held in Canada. The small pox vaccine was highly contested in the US but the Canadian government thought it was a good idea so they offered US scientists the option of coming here to vaccinate Canadian babies. This was in the 1950s and the vaccine seems to have been administered almost universally. That was a lot of Canadian babies. Thankfully, it seems to have worked out but it does seem mind-boggling today.

For all the indignation and shock we’re seeing, this is not the first time nor will it be the last time someone steps over a line in order to conduct scientific research. And, that is the eternal problem.

Meanwhile I think some of the real action regarding CRISPR and germline editing is taking place in the field (pun!) of agriculture:

My Nov. 27, 2018 posting titled: ‘Designer groundcherries by CRISPR (clustered regularly interspaced short palindromic repeats)‘ and a more disturbing Nov. 27, 2018 post titled: ‘Agriculture and gene editing … shades of the AquAdvantage salmon‘. That second posting features a company which is trying to sell its gene-editing services to farmers who would like cows that  never grow horns and pigs that never reach puberty.

Then there’s this ,

The Genetic Revolution‘, a documentary that offers relatively up-to-date information about gene editing, which was broadcast on Nov. 11, 2018 as part of The Nature of Things series on CBC (Canadian Broadcasting Corporation).

My July 17, 2018 posting about research suggesting that scientists hadn’t done enough research on possible effects of CRISPR editing titled: ‘The CRISPR ((clustered regularly interspaced short palindromic repeats)-CAS9 gene-editing technique may cause new genetic damage kerfuffle’.

My 2017 three-part series on CRISPR and germline editing:

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

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

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

There you have it.

Added on November 30, 2018: David Cyanowski has written one final article (Nov. 30, 2018 for Nature) about He and the Second International Summit on Human Genome Editing. He did not make his second scheduled appearance at the summit, returning to China before the summit concluded. He was rebuked in a statement produced by the Summit’s organizing committee at the end of the three-day meeting. The situation with regard to his professional status in China is ambiguous. Cyanowski ends his piece with the information that the third summit will take place in London (likely in the UK) in 2021. I encourage you to read Cyanowski’s Nov. 30, 2018 article in its entirety; it’s not long.

Added on Dec. 3, 2018: The story continues. Ed Yong has written a summary of the issues to date in a Dec. 3, 2018 article for The Atlantic (even if you know the story ift’s eyeopening to see all the parts put together.

J. Benjamin Hurlbut, Associate Professor of Life Sciences at Arizona State University (ASU) and Jason Scott Robert, Director of the Lincoln Center for Applied Ethics at Arizona State University have written a provocative (and true) Dec. 3, 2018 essay titled, CRISPR babies raise an uncomfortable reality – abiding by scientific standards doesn’t guarantee ethical research, for The Conversation. h/t phys.org

*[and from elsewhere] added January 17, 2019.

Added on January 23, 2019: He has been fired by his university (Southern University of Science and Technology in Shenzhen) as announced on January 21, 2019.  David Cyranoski provides a details accounting in his January 22, 2019 article for Nature.