Tag Archives: Massachusetts Institute of Technology

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.

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.

I found it at the movies: a commentary on/review of “Films from the Future”

Kudos to anyone who recognized the reference to Pauline Kael (she changed film criticism forever) and her book “I Lost it at the Movies.” Of course, her book title was a bit of sexual innuendo, quite risqué for an important film critic in 1965 but appropriate for a period (the 1960s) associated with a sexual revolution. (There’s more about the 1960’s sexual revolution in the US along with mention of a prior sexual revolution in the 1920s in this Wikipedia entry.)

The title for this commentary is based on an anecdote from Dr. Andrew Maynard’s (director of the Arizona State University [ASU] Risk Innovation Lab) popular science and technology book, “Films from the Future: The Technology and Morality of Sci-Fi Movies.”

The ‘title-inspiring’ anecdote concerns Maynard’s first viewing of ‘2001: A Space Odyssey, when as a rather “bratty” 16-year-old who preferred to read science fiction, he discovered new ways of seeing and imaging the world. Maynard isn’t explicit about when he became a ‘techno nerd’ or how movies gave him an experience books couldn’t but presumably at 16 he was already gearing up for a career in the sciences. That ‘movie’ revelation received in front of a black and white television on January 1,1982 eventually led him to write, “Films from the Future.” (He has a PhD in physics which he is now applying to the field of risk innovation. For a more detailed description of Dr. Maynard and his work, there’s his ASU profile webpage and, of course, the introduction to his book.)

The book is quite timely. I don’t know how many people have noticed but science and scientific innovation is being covered more frequently in the media than it has been in many years. Science fairs and festivals are being founded on what seems to be a daily basis and you can now find science in art galleries. (Not to mention the movies and television where science topics are covered in comic book adaptations, in comedy, and in standard science fiction style.) Much of this activity is centered on what’s called ’emerging technologies’. These technologies are why people argue for what’s known as ‘blue sky’ or ‘basic’ or ‘fundamental’ science for without that science there would be no emerging technology.

Films from the Future

Isn’t reading the Table of Contents (ToC) the best way to approach a book? (From Films from the Future; Note: The formatting has been altered),

Table of Contents
Chapter One
In the Beginning 14
Beginnings 14
Welcome to the Future 16
The Power of Convergence 18
Socially Responsible Innovation 21
A Common Point of Focus 25
Spoiler Alert 26
Chapter Two
Jurassic Park: The Rise of Resurrection Biology 27
When Dinosaurs Ruled the World 27
De-Extinction 31
Could We, Should We? 36
The Butterfly Effect 39
Visions of Power 43
Chapter Three
Never Let Me Go: A Cautionary Tale of Human Cloning 46
Sins of Futures Past 46
Cloning 51
Genuinely Human? 56
Too Valuable to Fail? 62
Chapter Four
Minority Report: Predicting Criminal Intent 64
Criminal Intent 64
The “Science” of Predicting Bad Behavior 69
Criminal Brain Scans 74
Machine Learning-Based Precognition 77
Big Brother, Meet Big Data 79
Chapter Five
Limitless: Pharmaceutically-enhanced Intelligence 86
A Pill for Everything 86
The Seduction of Self-Enhancement 89
Nootropics 91
If You Could, Would You? 97
Privileged Technology 101
Our Obsession with Intelligence 105
Chapter Six
Elysium: Social Inequity in an Age of Technological
Extremes 110
The Poor Shall Inherit the Earth 110
Bioprinting Our Future Bodies 115
The Disposable Workforce 119
Living in an Automated Future 124
Chapter Seven
Ghost in the Shell: Being Human in an
Augmented Future 129
Through a Glass Darkly 129
Body Hacking 135
More than “Human”? 137
Plugged In, Hacked Out 142
Your Corporate Body 147
Chapter Eight
Ex Machina: AI and the Art of Manipulation 154
Plato’s Cave 154
The Lure of Permissionless Innovation 160
Technologies of Hubris 164
Superintelligence 169
Defining Artificial Intelligence 172
Artificial Manipulation 175
Chapter Nine
Transcendence: Welcome to the Singularity 180
Visions of the Future 180
Technological Convergence 184
Enter the Neo-Luddites 190
Techno-Terrorism 194
Exponential Extrapolation 200
Make-Believe in the Age of the Singularity 203
Chapter Ten
The Man in the White Suit: Living in a Material World 208
There’s Plenty of Room at the Bottom 208
Mastering the Material World 213
Myopically Benevolent Science 220
Never Underestimate the Status Quo 224
It’s Good to Talk 227
Chapter Eleven
Inferno: Immoral Logic in an Age of
Genetic Manipulation 231
Decoding Make-Believe 231
Weaponizing the Genome 234
Immoral Logic? 238
The Honest Broker 242
Dictating the Future 248
Chapter Twelve
The Day After Tomorrow: Riding the Wave of
Climate Change 251
Our Changing Climate 251
Fragile States 255
A Planetary “Microbiome” 258
The Rise of the Anthropocene 260
Building Resiliency 262
Geoengineering the Future 266
Chapter Thirteen
Contact: Living by More than Science Alone 272
An Awful Waste of Space 272
More than Science Alone 277
Occam’s Razor 280
What If We’re Not Alone? 283
Chapter Fourteen
Looking to the Future 288
Acknowledgments 293

The ToC gives the reader a pretty clue as to where the author is going with their book and Maynard explains how he chose his movies in his introductory chapter (from Films from the Future),

“There are some quite wonderful science fiction movies that didn’t make the cut because they didn’t fit the overarching narrative (Blade Runner and its sequel Blade Runner 2049, for instance, and the first of the Matrix trilogy). There are also movies that bombed with the critics, but were included because they ably fill a gap in the bigger story around emerging and converging technologies. Ultimately, the movies that made the cut were chosen because, together, they create an overarching narrative around emerging trends in biotechnologies, cybertechnologies, and materials-based technologies, and they illuminate a broader landscape around our evolving relationship with science and technology. And, to be honest, they are all movies that I get a kick out of watching.” (p. 17)

Jurassic Park (Chapter Two)

Dinosaurs do not interest me—they never have. Despite my profound indifference I did see the movie, Jurassic Park, when it was first released (someone talked me into going). And, I am still profoundly indifferent. Thankfully, Dr. Maynard finds meaning and a connection to current trends in biotechnology,

Jurassic Park is unabashedly a movie about dinosaurs. But it’s also a movie about greed, ambition, genetic engineering, and human folly—all rich pickings for thinking about the future, and what could possibly go wrong. (p. 28)

What really stands out with Jurassic Park, over twenty-five years later, is how it reveals a very human side of science and technology. This comes out in questions around when we should tinker with technology and when we should leave well enough alone. But there is also a narrative here that appears time and time again with the movies in this book, and that is how we get our heads around the sometimes oversized roles mega-entrepreneurs play in dictating how new tech is used, and possibly abused. These are all issues that are just as relevant now as they were in 1993, and are front and center of ensuring that the technologyenabled future we’re building is one where we want to live, and not one where we’re constantly fighting for our lives.  (pp. 30-1)

He also describes a connection to current trends in biotechnology,

De-Extinction

In a far corner of Siberia, two Russians—Sergey Zimov and his son Nikita—are attempting to recreate the Ice Age. More precisely, their vision is to reconstruct the landscape and ecosystem of northern Siberia in the Pleistocene, a period in Earth’s history that stretches from around two and a half million years ago to eleven thousand years ago. This was a time when the environment was much colder than now, with huge glaciers and ice sheets flowing over much of the Earth’s northern hemisphere. It was also a time when humans
coexisted with animals that are long extinct, including saber-tooth cats, giant ground sloths, and woolly mammoths.

The Zimovs’ ambitions are an extreme example of “Pleistocene rewilding,” a movement to reintroduce relatively recently extinct large animals, or their close modern-day equivalents, to regions where they were once common. In the case of the Zimovs, the
father-and-son team believe that, by reconstructing the Pleistocene ecosystem in the Siberian steppes and elsewhere, they can slow down the impacts of climate change on these regions. These areas are dominated by permafrost, ground that never thaws through
the year. Permafrost ecosystems have developed and survived over millennia, but a warming global climate (a theme we’ll come back to in chapter twelve and the movie The Day After Tomorrow) threatens to catastrophically disrupt them, and as this happens, the impacts
on biodiversity could be devastating. But what gets climate scientists even more worried is potentially massive releases of trapped methane as the permafrost disappears.

Methane is a powerful greenhouse gas—some eighty times more effective at exacerbating global warming than carbon dioxide— and large-scale releases from warming permafrost could trigger catastrophic changes in climate. As a result, finding ways to keep it in the ground is important. And here the Zimovs came up with a rather unusual idea: maintaining the stability of the environment by reintroducing long-extinct species that could help prevent its destruction, even in a warmer world. It’s a wild idea, but one that has some merit.8 As a proof of concept, though, the Zimovs needed somewhere to start. And so they set out to create a park for deextinct Siberian animals: Pleistocene Park.9

Pleistocene Park is by no stretch of the imagination a modern-day Jurassic Park. The dinosaurs in Hammond’s park date back to the Mesozoic period, from around 250 million years ago to sixty-five million years ago. By comparison, the Pleistocene is relatively modern history, ending a mere eleven and a half thousand years ago. And the vision behind Pleistocene Park is not thrills, spills, and profit, but the serious use of science and technology to stabilize an increasingly unstable environment. Yet there is one thread that ties them together, and that’s using genetic engineering to reintroduce extinct species. In this case, the species in question is warm-blooded and furry: the woolly mammoth.

The idea of de-extinction, or bringing back species from extinction (it’s even called “resurrection biology” in some circles), has been around for a while. It’s a controversial idea, and it raises a lot of tough ethical questions. But proponents of de-extinction argue
that we’re losing species and ecosystems at such a rate that we can’t afford not to explore technological interventions to help stem the flow.

Early approaches to bringing species back from the dead have involved selective breeding. The idea was simple—if you have modern ancestors of a recently extinct species, selectively breeding specimens that have a higher genetic similarity to their forebears can potentially help reconstruct their genome in living animals. This approach is being used in attempts to bring back the aurochs, an ancestor of modern cattle.10 But it’s slow, and it depends on
the fragmented genome of the extinct species still surviving in its modern-day equivalents.

An alternative to selective breeding is cloning. This involves finding a viable cell, or cell nucleus, in an extinct but well-preserved animal and growing a new living clone from it. It’s definitely a more appealing route for impatient resurrection biologists, but it does mean getting your hands on intact cells from long-dead animals and devising ways to “resurrect” these, which is no mean feat. Cloning has potential when it comes to recently extinct species whose cells have been well preserved—for instance, where the whole animal has become frozen in ice. But it’s still a slow and extremely limited option.

Which is where advances in genetic engineering come in.

The technological premise of Jurassic Park is that scientists can reconstruct the genome of long-dead animals from preserved DNA fragments. It’s a compelling idea, if you think of DNA as a massively long and complex instruction set that tells a group of biological molecules how to build an animal. In principle, if we could reconstruct the genome of an extinct species, we would have the basic instruction set—the biological software—to reconstruct
individual members of it.

The bad news is that DNA-reconstruction-based de-extinction is far more complex than this. First you need intact fragments of DNA, which is not easy, as DNA degrades easily (and is pretty much impossible to obtain, as far as we know, for dinosaurs). Then you
need to be able to stitch all of your fragments together, which is akin to completing a billion-piece jigsaw puzzle without knowing what the final picture looks like. This is a Herculean task, although with breakthroughs in data manipulation and machine learning,
scientists are getting better at it. But even when you have your reconstructed genome, you need the biological “wetware”—all the stuff that’s needed to create, incubate, and nurture a new living thing, like eggs, nutrients, a safe space to grow and mature, and so on. Within all this complexity, it turns out that getting your DNA sequence right is just the beginning of translating that genetic code into a living, breathing entity. But in some cases, it might be possible.

In 2013, Sergey Zimov was introduced to the geneticist George Church at a conference on de-extinction. Church is an accomplished scientist in the field of DNA analysis and reconstruction, and a thought leader in the field of synthetic biology (which we’ll come
back to in chapter nine). It was a match made in resurrection biology heaven. Zimov wanted to populate his Pleistocene Park with mammoths, and Church thought he could see a way of
achieving this.

What resulted was an ambitious project to de-extinct the woolly mammoth. Church and others who are working on this have faced plenty of hurdles. But the technology has been advancing so fast that, as of 2017, scientists were predicting they would be able to reproduce the woolly mammoth within the next two years.

One of those hurdles was the lack of solid DNA sequences to work from. Frustratingly, although there are many instances of well preserved woolly mammoths, their DNA rarely survives being frozen for tens of thousands of years. To overcome this, Church and others
have taken a different tack: Take a modern, living relative of the mammoth, and engineer into it traits that would allow it to live on the Siberian tundra, just like its woolly ancestors.

Church’s team’s starting point has been the Asian elephant. This is their source of base DNA for their “woolly mammoth 2.0”—their starting source code, if you like. So far, they’ve identified fifty plus gene sequences they think they can play with to give their modern-day woolly mammoth the traits it would need to thrive in Pleistocene Park, including a coat of hair, smaller ears, and a constitution adapted to cold.

The next hurdle they face is how to translate the code embedded in their new woolly mammoth genome into a living, breathing animal. The most obvious route would be to impregnate a female Asian elephant with a fertilized egg containing the new code. But Asian elephants are endangered, and no one’s likely to allow such cutting edge experimentation on the precious few that are still around, so scientists are working on an artificial womb for their reinvented woolly mammoth. They’re making progress with mice and hope to crack the motherless mammoth challenge relatively soon.

It’s perhaps a stretch to call this creative approach to recreating a species (or “reanimation” as Church refers to it) “de-extinction,” as what is being formed is a new species. … (pp. 31-4)

This selection illustrates what Maynard does so very well throughout the book where he uses each film as a launching pad for a clear, readable description of relevant bits of science so you understand why the premise was likely, unlikely, or pure fantasy while linking it to contemporary practices, efforts, and issues. In the context of Jurassic Park, Maynard goes on to raise some fascinating questions such as: Should we revive animals rendered extinct (due to obsolescence or inability to adapt to new conditions) when we could develop new animals?

General thoughts

‘Films for the Future’ offers readable (to non-scientific types) science, lively writing, and the occasional ‘memorish’ anecdote. As well, Dr. Maynard raises the curtain on aspects of the scientific enterprise that most of us do not get to see.  For example, the meeting  between Sergey Zimov and George Church and how it led to new ‘de-extinction’ work’. He also describes the problems that the scientists encountered and are encountering. This is in direct contrast to how scientific work is usually presented in the news media as one glorious breakthrough after the next.

Maynard does discuss the issues of social inequality and power and ownership. For example, who owns your transplant or data? Puzzlingly, he doesn’t touch on the current environment where scientists in the US and elsewhere are encouraged/pressured to start up companies commercializing their work.

Nor is there any mention of how universities are participating in this grand business experiment often called ‘innovation’. (My March 15, 2017 posting describes an outcome for the CRISPR [gene editing system] patent fight taking place between Harvard University’s & MIT’s [Massachusetts Institute of Technology] Broad Institute vs the University of California at Berkeley and my Sept. 11, 2018 posting about an art/science exhibit in Vancouver [Canada] provides an update for round 2 of the Broad Institute vs. UC Berkeley patent fight [scroll down about 65% of the way.) *To read about how my ‘cultural blindness’ shows up here scroll down to the single asterisk at the end.*

There’s a foray through machine-learning and big data as applied to predictive policing in Maynard’s ‘Minority Report’ chapter (my November 23, 2017 posting describes Vancouver’s predictive policing initiative [no psychics involved], the first such in Canada). There’s no mention of surveillance technology, which if I recall properly was part of the future environment, both by the state and by corporations. (Mia Armstrong’s November 15, 2018 article for Slate on Chinese surveillance being exported to Venezuela provides interesting insight.)

The gaps are interesting and various. This of course points to a problem all science writers have when attempting an overview of science. (Carl Zimmer’s latest, ‘She Has Her Mother’s Laugh: The Powers, Perversions, and Potential of Heredity’] a doorstopping 574 pages, also has some gaps despite his focus on heredity,)

Maynard has worked hard to give an comprehensive overview in a remarkably compact 279 pages while developing his theme about science and the human element. In other words, science is not monolithic; it’s created by human beings and subject to all the flaws and benefits that humanity’s efforts are always subject to—scientists are people too.

The readership for ‘Films from the Future’ spans from the mildly interested science reader to someone like me who’s been writing/blogging about these topics (more or less) for about 10 years. I learned a lot reading this book.

Next time, I’m hopeful there’ll be a next time, Maynard might want to describe the parameters he’s set for his book in more detail that is possible in his chapter headings. He could have mentioned that he’s not a cinéaste so his descriptions of the movies are very much focused on the story as conveyed through words. He doesn’t mention colour palates, camera angles, or, even, cultural lenses.

Take for example, his chapter on ‘Ghost in the Shell’. Focused on the Japanese animation film and not the live action Hollywood version he talks about human enhancement and cyborgs. The Japanese have a different take on robots, inanimate objects, and, I assume, cyborgs than is found in Canada or the US or Great Britain, for that matter (according to a colleague of mine, an Englishwoman who lived in Japan for ten or more years). There’s also the chapter on the Ealing comedy, The Man in The White Suit, an English film from the 1950’s. That too has a cultural (as well as, historical) flavour but since Maynard is from England, he may take that cultural flavour for granted. ‘Never let me go’ in Chapter Two was also a UK production, albeit far more recent than the Ealing comedy and it’s interesting to consider how a UK production about cloning might differ from a US or Chinese or … production on the topic. I am hearkening back to Maynard’s anecdote about movies giving him new ways of seeing and imagining the world.

There’s a corrective. A couple of sentences in Maynard’s introductory chapter cautioning that in depth exploration of ‘cultural lenses’ was not possible without expanding the book to an unreadable size followed by a sentence in each of the two chapters that there are cultural differences.

One area where I had a significant problem was with regard to being “programmed” and having  “instinctual” behaviour,

As a species, we are embarrassingly programmed to see “different” as “threatening,” and to take instinctive action against it. It’s a trait that’s exploited in many science fiction novels and movies, including those in this book. If we want to see the rise of increasingly augmented individuals, we need to be prepared for some social strife. (p. 136)

These concepts are much debated in the social sciences and there are arguments for and against ‘instincts regarding strangers and their possible differences’. I gather Dr. Maynard hies to the ‘instinct to defend/attack’ school of thought.

One final quandary, there was no sex and I was expecting it in the Ex Machina chapter, especially now that sexbots are about to take over the world (I exaggerate). Certainly, if you’re talking about “social strife,” then sexbots would seem to be fruitful line of inquiry, especially when there’s talk of how they could benefit families (my August 29, 2018 posting). Again, there could have been a sentence explaining why Maynard focused almost exclusively in this chapter on the discussions about artificial intelligence and superintelligence.

Taken in the context of the book, these are trifling issues and shouldn’t stop you from reading Films from the Future. What Maynard has accomplished here is impressive and I hope it’s just the beginning.

Final note

Bravo Andrew! (Note: We’ve been ‘internet acquaintances/friends since the first year I started blogging. When I’m referring to him in his professional capacity, he’s Dr. Maynard and when it’s not strictly in his professional capacity, it’s Andrew. For this commentary/review I wanted to emphasize his professional status.)

If you need to see a few more samples of Andrew’s writing, there’s a Nov. 15, 2018 essay on The Conversation, Sci-fi movies are the secret weapon that could help Silicon Valley grow up and a Nov. 21, 2018 article on slate.com, The True Cost of Stain-Resistant Pants; The 1951 British comedy The Man in the White Suit anticipated our fears about nanotechnology. Enjoy.

****Added at 1700 hours on Nov. 22, 2018: You can purchase Films from the Future here.

*Nov. 23, 2018: I should have been more specific and said ‘academic scientists’. In Canada, the great percentage of scientists are academic. It’s to the point where the OECD (Organization for Economic Cooperation and Development) has noted that amongst industrialized countries, Canada has very few industrial scientists in comparison to the others.

Café Scientifique Vancouver (Canada) talk on October 30th, 2018: Solving some of Canada’s grandest challenges with synthetic biology

From an October 16, 2018 Café Scientifique Vancouver announcement (received via email),

Our next café will happen on TUESDAY, OCTOBER 30TH at 7:30PM in the
back room at YAGGER’S DOWNTOWN (433 W Pender). Our speaker for the
evening will be DR. VIKRAMADITYA G. YADAV. His topic will be:

SOLVING SOME OF CANADA’S GRANDEST CHALLENGES WITH SYNTHETIC BIOLOGY

A warming climate, unrepressed mining and logging, contamination of our
water resources, the uncertain price and tight supply of crude oil and
the growing threat of epidemics are having a profound, negative impact
on the well-being of Canadians. There is an urgent need to develop and
implement sustainable manufacturing technologies that can not only meet
our material and energy needs, but also sustain our quality of life.
Romantic and unbelievable as it sounds, Nature posses all the answer to
our challenges, and the coming decades in science and engineering will
be typified by our attempts to mimic or recruit biology to address our
needs. This talk will present a vivid snapshot of current and emerging
research towards this goal and highlight some cutting-edge technologies
under development at the University of British Columbia [UBC].

When he joined the University of Waterloo as an undergraduate student in
chemical engineering, Dr. Vikramaditya G. Yadav coveted a career in
Alberta’s burgeoning petrochemical sector. He even interned at Imperial
Oil during his first summer break from university. Then, one fine
evening during second year, he stumbled upon a copy of Juan Enríquez’s
As the Future Catches You in the library and became instantly captivated
with biological engineering. His journey over the past few years has
taken him to Sanofi Pasteur [vaccines division of the multinational
pharmaceutical
company Sanofi], the Massachusetts Institute of Technology [MIT],
Harvard University, and finally, the University of British Columbia,
where he now leads a wonderful group of researchers working on
wide-ranging topics at the interface of biology, chemistry, engineering,
medicine and economics.

We hope to see you there!

Oftentimes, the speaker is asked to write up a description of their talk and assuming that’s the case and based on how it’s written, I’d say the odds are good that this will be a lively, engaging talk.

For more proof, you can check out Dr. Yadav’s description of his research interests on his UBC profile page. BTW, his research group is called The Biofoundry (at UBC).

A 3D printed eye cornea and a 3D printed copy of your brain (also: a Brad Pitt connection)

Sometimes it’s hard to keep up with 3D tissue printing news. I have two news bits, one concerning eyes and another concerning brains.

3D printed human corneas

A May 29, 2018 news item on ScienceDaily trumpets the news,

The first human corneas have been 3D printed by scientists at Newcastle University, UK.

It means the technique could be used in the future to ensure an unlimited supply of corneas.

As the outermost layer of the human eye, the cornea has an important role in focusing vision.

Yet there is a significant shortage of corneas available to transplant, with 10 million people worldwide requiring surgery to prevent corneal blindness as a result of diseases such as trachoma, an infectious eye disorder.

In addition, almost 5 million people suffer total blindness due to corneal scarring caused by burns, lacerations, abrasion or disease.

The proof-of-concept research, published today [May 29, 2018] in Experimental Eye Research, reports how stem cells (human corneal stromal cells) from a healthy donor cornea were mixed together with alginate and collagen to create a solution that could be printed, a ‘bio-ink’.

Here are the proud researchers with their cornea,

Caption: Dr. Steve Swioklo and Professor Che Connon with a dyed cornea. Credit: Newcastle University, UK

A May 30,2018 Newcastle University press release (also on EurekAlert but published on May 29, 2018), which originated the news item, adds more details,

Using a simple low-cost 3D bio-printer, the bio-ink was successfully extruded in concentric circles to form the shape of a human cornea. It took less than 10 minutes to print.

The stem cells were then shown to culture – or grow.

Che Connon, Professor of Tissue Engineering at Newcastle University, who led the work, said: “Many teams across the world have been chasing the ideal bio-ink to make this process feasible.

“Our unique gel – a combination of alginate and collagen – keeps the stem cells alive whilst producing a material which is stiff enough to hold its shape but soft enough to be squeezed out the nozzle of a 3D printer.

“This builds upon our previous work in which we kept cells alive for weeks at room temperature within a similar hydrogel. Now we have a ready to use bio-ink containing stem cells allowing users to start printing tissues without having to worry about growing the cells separately.”

The scientists, including first author and PhD student Ms Abigail Isaacson from the Institute of Genetic Medicine, Newcastle University, also demonstrated that they could build a cornea to match a patient’s unique specifications.

The dimensions of the printed tissue were originally taken from an actual cornea. By scanning a patient’s eye, they could use the data to rapidly print a cornea which matched the size and shape.

Professor Connon added: “Our 3D printed corneas will now have to undergo further testing and it will be several years before we could be in the position where we are using them for transplants.

“However, what we have shown is that it is feasible to print corneas using coordinates taken from a patient eye and that this approach has potential to combat the world-wide shortage.”

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

3D bioprinting of a corneal stroma equivalent by Abigail Isaacson, Stephen Swioklo, Che J. Connon. Experimental Eye Research Volume 173, August 2018, Pages 188–193 and 2018 May 14 pii: S0014-4835(18)30212-4. doi: 10.1016/j.exer.2018.05.010. [Epub ahead of print]

This paper is behind a paywall.

A 3D printed copy of your brain

I love the title for this May 30, 2018 Wyss Institute for Biologically Inspired Engineering news release: Creating piece of mind by Lindsay Brownell (also on EurekAlert),

What if you could hold a physical model of your own brain in your hands, accurate down to its every unique fold? That’s just a normal part of life for Steven Keating, Ph.D., who had a baseball-sized tumor removed from his brain at age 26 while he was a graduate student in the MIT Media Lab’s Mediated Matter group. Curious to see what his brain actually looked like before the tumor was removed, and with the goal of better understanding his diagnosis and treatment options, Keating collected his medical data and began 3D printing his MRI [magnetic resonance imaging] and CT [computed tomography] scans, but was frustrated that existing methods were prohibitively time-intensive, cumbersome, and failed to accurately reveal important features of interest. Keating reached out to some of his group’s collaborators, including members of the Wyss Institute at Harvard University, who were exploring a new method for 3D printing biological samples.

“It never occurred to us to use this approach for human anatomy until Steve came to us and said, ‘Guys, here’s my data, what can we do?” says Ahmed Hosny, who was a Research Fellow with at the Wyss Institute at the time and is now a machine learning engineer at the Dana-Farber Cancer Institute. The result of that impromptu collaboration – which grew to involve James Weaver, Ph.D., Senior Research Scientist at the Wyss Institute; Neri Oxman, [emphasis mine] Ph.D., Director of the MIT Media Lab’s Mediated Matter group and Associate Professor of Media Arts and Sciences; and a team of researchers and physicians at several other academic and medical centers in the US and Germany – is a new technique that allows images from MRI, CT, and other medical scans to be easily and quickly converted into physical models with unprecedented detail. The research is reported in 3D Printing and Additive Manufacturing.

“I nearly jumped out of my chair when I saw what this technology is able to do,” says Beth Ripley, M.D. Ph.D., an Assistant Professor of Radiology at the University of Washington and clinical radiologist at the Seattle VA, and co-author of the paper. “It creates exquisitely detailed 3D-printed medical models with a fraction of the manual labor currently required, making 3D printing more accessible to the medical field as a tool for research and diagnosis.”

Imaging technologies like MRI and CT scans produce high-resolution images as a series of “slices” that reveal the details of structures inside the human body, making them an invaluable resource for evaluating and diagnosing medical conditions. Most 3D printers build physical models in a layer-by-layer process, so feeding them layers of medical images to create a solid structure is an obvious synergy between the two technologies.

However, there is a problem: MRI and CT scans produce images with so much detail that the object(s) of interest need to be isolated from surrounding tissue and converted into surface meshes in order to be printed. This is achieved via either a very time-intensive process called “segmentation” where a radiologist manually traces the desired object on every single image slice (sometimes hundreds of images for a single sample), or an automatic “thresholding” process in which a computer program quickly converts areas that contain grayscale pixels into either solid black or solid white pixels, based on a shade of gray that is chosen to be the threshold between black and white. However, medical imaging data sets often contain objects that are irregularly shaped and lack clear, well-defined borders; as a result, auto-thresholding (or even manual segmentation) often over- or under-exaggerates the size of a feature of interest and washes out critical detail.

The new method described by the paper’s authors gives medical professionals the best of both worlds, offering a fast and highly accurate method for converting complex images into a format that can be easily 3D printed. The key lies in printing with dithered bitmaps, a digital file format in which each pixel of a grayscale image is converted into a series of black and white pixels, and the density of the black pixels is what defines the different shades of gray rather than the pixels themselves varying in color.

Similar to the way images in black-and-white newsprint use varying sizes of black ink dots to convey shading, the more black pixels that are present in a given area, the darker it appears. By simplifying all pixels from various shades of gray into a mixture of black or white pixels, dithered bitmaps allow a 3D printer to print complex medical images using two different materials that preserve all the subtle variations of the original data with much greater accuracy and speed.

The team of researchers used bitmap-based 3D printing to create models of Keating’s brain and tumor that faithfully preserved all of the gradations of detail present in the raw MRI data down to a resolution that is on par with what the human eye can distinguish from about 9-10 inches away. Using this same approach, they were also able to print a variable stiffness model of a human heart valve using different materials for the valve tissue versus the mineral plaques that had formed within the valve, resulting in a model that exhibited mechanical property gradients and provided new insights into the actual effects of the plaques on valve function.

“Our approach not only allows for high levels of detail to be preserved and printed into medical models, but it also saves a tremendous amount of time and money,” says Weaver, who is the corresponding author of the paper. “Manually segmenting a CT scan of a healthy human foot, with all its internal bone structure, bone marrow, tendons, muscles, soft tissue, and skin, for example, can take more than 30 hours, even by a trained professional – we were able to do it in less than an hour.”

The researchers hope that their method will help make 3D printing a more viable tool for routine exams and diagnoses, patient education, and understanding the human body. “Right now, it’s just too expensive for hospitals to employ a team of specialists to go in and hand-segment image data sets for 3D printing, except in extremely high-risk or high-profile cases. We’re hoping to change that,” says Hosny.

In order for that to happen, some entrenched elements of the medical field need to change as well. Most patients’ data are compressed to save space on hospital servers, so it’s often difficult to get the raw MRI or CT scan files needed for high-resolution 3D printing. Additionally, the team’s research was facilitated through a joint collaboration with leading 3D printer manufacturer Stratasys, which allowed access to their 3D printer’s intrinsic bitmap printing capabilities. New software packages also still need to be developed to better leverage these capabilities and make them more accessible to medical professionals.

Despite these hurdles, the researchers are confident that their achievements present a significant value to the medical community. “I imagine that sometime within the next 5 years, the day could come when any patient that goes into a doctor’s office for a routine or non-routine CT or MRI scan will be able to get a 3D-printed model of their patient-specific data within a few days,” says Weaver.

Keating, who has become a passionate advocate of efforts to enable patients to access their own medical data, still 3D prints his MRI scans to see how his skull is healing post-surgery and check on his brain to make sure his tumor isn’t coming back. “The ability to understand what’s happening inside of you, to actually hold it in your hands and see the effects of treatment, is incredibly empowering,” he says.

“Curiosity is one of the biggest drivers of innovation and change for the greater good, especially when it involves exploring questions across disciplines and institutions. The Wyss Institute is proud to be a space where this kind of cross-field innovation can flourish,” says 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).

Here’s an image illustrating the work,

Caption: This 3D-printed model of Steven Keating’s skull and brain clearly shows his brain tumor and other fine details thanks to the new data processing method pioneered by the study’s authors. Credit: Wyss Institute at Harvard University

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

From Improved Diagnostics to Presurgical Planning: High-Resolution Functionally Graded Multimaterial 3D Printing of Biomedical Tomographic Data Sets by Ahmed Hosny , Steven J. Keating, Joshua D. Dilley, Beth Ripley, Tatiana Kelil, Steve Pieper, Dominik Kolb, Christoph Bader, Anne-Marie Pobloth, Molly Griffin, Reza Nezafat, Georg Duda, Ennio A. Chiocca, James R.. Stone, James S. Michaelson, Mason N. Dean, Neri Oxman, and James C. Weaver. 3D Printing and Additive Manufacturing http://doi.org/10.1089/3dp.2017.0140 Online Ahead of Print:May 29, 2018

This paper appears to be open access.

A tangential Brad Pitt connection

It’s a bit of Hollywood gossip. There was some speculation in April 2018 that Brad Pitt was dating Dr. Neri Oxman highlighted in the Wyss Institute news release. Here’s a sample of an April 13, 2018 posting on Laineygossip (Note: A link has been removed),

It took him a long time to date, but he is now,” the insider tells PEOPLE. “He likes women who challenge him in every way, especially in the intellect department. Brad has seen how happy and different Amal has made his friend (George Clooney). It has given him something to think about.”

While a Pitt source has maintained he and Oxman are “just friends,” they’ve met up a few times since the fall and the insider notes Pitt has been flying frequently to the East Coast. He dropped by one of Oxman’s classes last fall and was spotted at MIT again a few weeks ago.

Pitt and Oxman got to know each other through an architecture project at MIT, where she works as a professor of media arts and sciences at the school’s Media Lab. Pitt has always been interested in architecture and founded the Make It Right Foundation, which builds affordable and environmentally friendly homes in New Orleans for people in need.

“One of the things Brad has said all along is that he wants to do more architecture and design work,” another source says. “He loves this, has found the furniture design and New Orleans developing work fulfilling, and knows he has a talent for it.”

It’s only been a week since Page Six first broke the news that Brad and Dr Oxman have been spending time together.

I’m fascinated by Oxman’s (and her colleagues’) furniture. Rose Brook writes about one particular Oxman piece in her March 27, 2014 posting for TCT magazine (Note: Links have been removed),

MIT Professor and 3D printing forerunner Neri Oxman has unveiled her striking acoustic chaise longue, which was made using Stratasys 3D printing technology.

Oxman collaborated with Professor W Craig Carter and Composer and fellow MIT Professor Tod Machover to explore material properties and their spatial arrangement to form the acoustic piece.

Christened Gemini, the two-part chaise was produced using a Stratasys Objet500 Connex3 multi-colour, multi-material 3D printer as well as traditional furniture-making techniques and it will be on display at the Vocal Vibrations exhibition at Le Laboratoire in Paris from March 28th 2014.

An Architect, Designer and Professor of Media, Arts and Science at MIT, Oxman’s creation aims to convey the relationship of twins in the womb through material properties and their arrangement. It was made using both subtractive and additive manufacturing and is part of Oxman’s ongoing exploration of what Stratasys’ ground-breaking multi-colour, multi-material 3D printer can do.

Brook goes on to explain how the chaise was made and the inspiration that led to it. Finally, it’s interesting to note that Oxman was working with Stratasys in 2014 and that this 2018 brain project is being developed in a joint collaboration with Statasys.

That’s it for 3D printing today.

Santiago Ramón y Cajal and the butterflies of the soul

The Cajal exhibit of drawings was here in Vancouver (Canada) this last fall (2017) and I still carry the memory of that glorious experience (see my Sept. 11, 2017 posting for more about the show and associated events). It seems Cajal’s drawings had a similar response in New York city, from a January 18, 2018 article by Roberta Smith for the New York Times,

It’s not often that you look at an exhibition with the help of the very apparatus that is its subject. But so it is with “The Beautiful Brain: The Drawings of Santiago Ramón y Cajal” at the Grey Art Gallery at New York University, one of the most unusual, ravishing exhibitions of the season.

The show finished its run on March 31, 2018 and is now on its way to the Massachusetts Institute of Technology (MIT) in Boston, Massachusetts for its opening on May 3, 2018. It looks like they have an exciting lineup of events to go along with the exhibit (from MIT’s The Beautiful Brain: The Drawings of Santiago Ramón y Cajal exhibit and event page),

SUMMER PROGRAMS

ONGOING

Spotlight Tours
Explorations led by local and Spanish scientists, artists, and entrepreneurs who will share their unique perspectives on particular aspects of the exhibition. (2:00 pm on select Tuesdays and Saturdays)

Tue, May 8 – Mark Harnett, Fred and Carole Middleton Career Development Professor at MIT and McGovern Institute Investigator Sat, May 26 – Marion Boulicault, MIT Graduate Student and Neuroethics Fellow in the Center for Sensorimotor Neural Engineering Tue, June 5 – Kelsey Allen, Graduate researcher, MIT Center for Brains, Minds, and Machines Sat, Jun 23 – Francisco Martin-Martinez, Research Scientist in MIT’s Laboratory for Atomistic & Molecular Mechanics and President of the Spanish Foundation for Science and Technology Jul 21 – Alex Gomez-Marin, Principal Investigator of the Behavior of Organisms Laboratory in the Instituto de Neurociencias, Spain Tue, Jul 31– Julie Pryor, Director of Communications at the McGovern Institute for Brain Research at MIT Tue, Aug 28 – Satrajit Ghosh, Principal Research Scientist at the McGovern Institute for Brain Research at MIT, Assistant Professor in the Department of Otolaryngology at Harvard Medical School, and faculty member in the Speech and Hearing Biosciences and Technology program in the Harvard Division of Medical Sciences

Idea Hub
Drop in and explore expansion microscopy in our maker-space.

Visualizing Science Workshop
Experiential learning with micro-scale biological images. (pre-registration required)

Gallery Demonstrations
Researchers share the latest on neural anatomy, signal transmission, and modern imaging techniques.

EVENTS

Teen Science Café: Mindful Matters
MIT researchers studying the brain share their mind-blowing findings.

Neuron Paint Night
Create a painting of cerebral cortex neurons and learn about the EyeWire citizen science game.

Cerebral Cinema Series
Hear from researchers and then compare real science to depictions on the big screen.

Brainy Trivia
Test your brain power in a night of science trivia and short, snappy research talks.

Come back to see our exciting lineup for the fall!

If you don’t have a chance to see the show or if you’d like a preview, I encourage you to read Smith’s article as it has embedded several Cajal drawings and rendered them exceptionally well.

For those who like a little contemporary (and related) science with their art, there’s a March 30, 2018 Harvard Medical Schoo (HMS)l news release by Kevin Jang (also on EurekAlert), Note: All links save one have been removed,

Drawing of the cells of the chick cerebellum by Santiago Ramón y Cajal, from “Estructura de los centros nerviosos de las aves,” Madrid, circa 1905

 

Modern neuroscience, for all its complexity, can trace its roots directly to a series of pen-and-paper sketches rendered by Nobel laureate Santiago Ramón y Cajal in the late 19th and early 20th centuries.

His observations and drawings exposed the previously hidden composition of the brain, revealing neuronal cell bodies and delicate projections that connect individual neurons together into intricate networks.

As he explored the nervous systems of various organisms under his microscope, a natural question arose: What makes a human brain different from the brain of any other species?

At least part of the answer, Ramón y Cajal hypothesized, lay in a specific class of neuron—one found in a dazzling variety of shapes and patterns of connectivity, and present in higher proportions in the human brain than in the brains of other species. He dubbed them the “butterflies of the soul.”

Known as interneurons, these cells play critical roles in transmitting information between sensory and motor neurons, and, when defective, have been linked to diseases such as schizophrenia, autism and intellectual disability.

Despite more than a century of study, however, it remains unclear why interneurons are so diverse and what specific functions the different subtypes carry out.

Now, in a study published in the March 22 [2018] issue of Nature, researchers from Harvard Medical School, New York Genome Center, New York University and the Broad Institute of MIT and Harvard have detailed for the first time how interneurons emerge and diversify in the brain.

Using single-cell analysis—a technology that allows scientists to track cellular behavior one cell at a time—the team traced the lineage of interneurons from their earliest precursor states to their mature forms in mice. The researchers identified key genetic programs that determine the fate of developing interneurons, as well as when these programs are switched on or off.

The findings serve as a guide for efforts to shed light on interneuron function and may help inform new treatment strategies for disorders involving their dysfunction, the authors said.

“We knew more than 100 years ago that this huge diversity of morphologically interesting cells existed in the brain, but their specific individual roles in brain function are still largely unclear,” said co-senior author Gordon Fishell, HMS professor of neurobiology and a faculty member at the Stanley Center for Psychiatric Research at the Broad.

“Our study provides a road map for understanding how and when distinct interneuron subtypes develop, giving us unprecedented insight into the biology of these cells,” he said. “We can now investigate interneuron properties as they emerge, unlock how these important cells function and perhaps even intervene when they fail to develop correctly in neuropsychiatric disease.”

A hippocampal interneuron. Image: Biosciences Imaging Gp, Soton, Wellcome Trust via Creative CommonsA hippocampal interneuron. Image: Biosciences Imaging Gp, Soton, Wellcome Trust via Creative Commons

Origins and Fates

In collaboration with co-senior author Rahul Satija, core faculty member of the New York Genome Center, Fishell and colleagues analyzed brain regions in developing mice known to contain precursor cells that give rise to interneurons.

Using Drop-seq, a single-cell sequencing technique created by researchers at HMS and the Broad, the team profiled gene expression in thousands of individual cells at multiple time points.

This approach overcomes a major limitation in past research, which could analyze only the average activity of mixtures of many different cells.

In the current study, the team found that the precursor state of all interneurons had similar gene expression patterns despite originating in three separate brain regions and giving rise to 14 or more interneuron subtypes alone—a number still under debate as researchers learn more about these cells.

“Mature interneuron subtypes exhibit incredible diversity. Their morphology and patterns of connectivity and activity are so different from each other, but our results show that the first steps in their maturation are remarkably similar,” said Satija, who is also an assistant professor of biology at New York University.

“They share a common developmental trajectory at the earliest stages, but the seeds of what will cause them to diverge later—a handful of genes—are present from the beginning,” Satija said.

As they profiled cells at later stages in development, the team observed the initial emergence of four interneuron “cardinal” classes, which give rise to distinct fates. Cells were committed to these fates even in the early embryo. By developing a novel computational strategy to link precursors with adult subtypes, the researchers identified individual genes that were switched on and off when cells began to diversify.

For example, they found that the gene Mef2c—mutations of which are linked to Alzheimer’s disease, schizophrenia and neurodevelopmental disorders in humans—is an early embryonic marker for a specific interneuron subtype known as Pvalb neurons. When they deleted Mef2c in animal models, Pvalb neurons failed to develop.

These early genes likely orchestrate the execution of subsequent genetic subroutines, such as ones that guide interneuron subtypes as they migrate to different locations in the brain and ones that help form unique connection patterns with other neural cell types, the authors said.

The identification of these genes and their temporal activity now provide researchers with specific targets to investigate the precise functions of interneurons, as well as how neurons diversify in general, according to the authors.

“One of the goals of this project was to address an incredibly fascinating developmental biology question, which is how individual progenitor cells decide between different neuronal fates,” Satija said. “In addition to these early markers of interneuron divergence, we found numerous additional genes that increase in expression, many dramatically, at later time points.”

The association of some of these genes with neuropsychiatric diseases promises to provide a better understanding of these disorders and the development of therapeutic strategies to treat them, a particularly important notion given the paucity of new treatments, the authors said.

Over the past 50 years, there have been no fundamentally new classes of neuropsychiatric drugs, only newer versions of old drugs, the researchers pointed out.

“Our repertoire is no better than it was in the 1970s,” Fishell said.

“Neuropsychiatric diseases likely reflect the dysfunction of very specific cell types. Our study puts forward a clear picture of what cells to look at as we work to shed light on the mechanisms that underlie these disorders,” Fishell said. “What we will find remains to be seen, but we have new, strong hypotheses that we can now test.”

As a resource for the research community, the study data and software are open-source and freely accessible online.

A gallery of the drawings of Santiago Ramón y Cajal is currently on display in New York City, and will open at the MIT Museum in Boston in May 2018.

Christian Mayer, Christoph Hafemeister and Rachel Bandler served as co-lead authors on the study.

This work was supported by the National Institutes of Health (R01 NS074972, R01 NS081297, MH071679-12, DP2-HG-009623, F30MH114462, T32GM007308, F31NS103398), the European Molecular Biology Organization, the National Science Foundation and the Simons Foundation.

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

Developmental diversification of cortical inhibitory interneurons by Christian Mayer, Christoph Hafemeister, Rachel C. Bandler, Robert Machold, Renata Batista Brito, Xavier Jaglin, Kathryn Allaway, Andrew Butler, Gord Fishell, & Rahul Satija. Nature volume 555, pages 457–462 (22 March 2018) doi:10.1038/nature25999 Published: 05 March 2018

This paper is behind a paywall.