I love this lobster. In most photos, they’re food. This shows off the lobster as a living entity while showcasing its underbelly, which is what this story is all about. From an April 23, 2021 news item on phys.org (Note: A link has been removed),
A lobster’s underbelly is lined with a thin, translucent membrane that is both stretchy and surprisingly tough. This marine under-armor, as MIT [Massachusetts Institute of Technology] engineers reported in 2019, is made from the toughest known hydrogel in nature, which also happens to be highly flexible. This combination of strength and stretch helps shield a lobster as it scrabbles across the seafloor, while also allowing it to flex back and forth to swim.
Now a separate MIT team has fabricated a hydrogel-based material that mimics the structure of the lobster’s underbelly. The researchers ran the material through a battery of stretch and impact tests, and showed that, similar to the lobster underbelly, the synthetic material is remarkably “fatigue-resistant,” able to withstand repeated stretches and strains without tearing.
If the fabrication process could be significantly scaled up, materials made from nanofibrous hydrogels could be used to make stretchy and strong replacement tissues such as artificial tendons and ligaments.
The team’s results are published in the journal Matter. The paper’s MIT co-authors include postdocs Jiahua Ni and Shaoting Lin; graduate students Xinyue Liu and Yuchen Sun; professor of aeronautics and astronautics Raul Radovitzky; professor of chemistry Keith Nelson; mechanical engineering professor Xuanhe Zhao; and former research scientist David Veysset Ph.D. ’16, now at Stanford University; along with Zhao Qin, assistant professor at Syracuse University, and Alex Hsieh of the Army Research Laboratory.
An April 23, 2021 MIT news release (also on EurekAlert) by Jennifer Chu, which originated the news item, offers an overview of the groundwork for this latest research along with technical detail about the latest work,
In 2019, Lin and other members of Zhao’s group developed a new kind of fatigue-resistant material made from hydrogel — a gelatin-like class of materials made primarily of water and cross-linked polymers. They fabricated the material from ultrathin fibers of hydrogel, which aligned like many strands of gathered straw when the material was repeatedly stretched. This workout also happened to increase the hydrogel’s fatigue resistance.
“At that moment, we had a feeling nanofibers in hydrogels were important, and hoped to manipulate the fibril structures so that we could optimize fatigue resistance,” says Lin.
In their new study, the researchers combined a number of techniques to create stronger hydrogel nanofibers. The process starts with electrospinning, a fiber production technique that uses electric charges to draw ultrathin threads out of polymer solutions. The team used high-voltage charges to spin nanofibers from a polymer solution, to form a flat film of nanofibers, each measuring about 800 nanometers — a fraction of the diameter of a human hair.
They placed the film in a high-humidity chamber to weld the individual fibers into a sturdy, interconnected network, and then set the film in an incubator to crystallize the individual nanofibers at high temperatures, further strengthening the material.
They tested the film’s fatigue-resistance by placing it in a machine that stretched it repeatedly over tens of thousands of cycles. They also made notches in some films and observed how the cracks propagated as the films were stretched repeatedly. From these tests, they calculated that the nanofibrous films were 50 times more fatigue-resistant than the conventional nanofibrous hydrogels.
Around this time, they read with interest a study by Ming Guo, associate professor of mechanical engineering at MIT, who characterized the mechanical properties of a lobster’s underbelly. This protective membrane is made from thin sheets of chitin, a natural, fibrous material that is similar in makeup to the group’s hydrogel nanofibers.
Guo found that a cross-section of the lobster membrane revealed sheets of chitin stacked at 36-degree angles, similar to twisted plywood, or a spiral staircase. This rotating, layered configuration, known as a bouligand structure, enhanced the membrane’s properties of stretch and strength.
“We learned that this bouligand structure in the lobster underbelly has high mechanical performance, which motivated us to see if we could reproduce such structures in synthetic materials,” Lin says.
Ni, Lin, and members of Zhao’s group teamed up with Nelson’s lab and Radovitzky’s group in MIT’s Institute for Soldier Nanotechnologies, and Qin’s lab at Syracuse University, to see if they could reproduce the lobster’s bouligand membrane structure using their synthetic, fatigue-resistant films.
“We prepared aligned nanofibers by electrospinning to mimic the chinic fibers existed in the lobster underbelly,” Ni says.
After electrospinning nanofibrous films, the researchers stacked each of five films in successive, 36-degree angles to form a single bouligand structure, which they then welded and crystallized to fortify the material. The final product measured 9 square centimeters and about 30 to 40 microns thick — about the size of a small piece of Scotch tape.
Stretch tests showed that the lobster-inspired material performed similarly to its natural counterpart, able to stretch repeatedly while resisting tears and cracks — a fatigue-resistance Lin attributes to the structure’s angled architecture.
“Intuitively, once a crack in the material propagates through one layer, it’s impeded by adjacent layers, where fibers are aligned at different angles,” Lin explains.
The team also subjected the material to microballistic impact tests with an experiment designed by Nelson’s group. They imaged the material as they shot it with microparticles at high velocity, and measured the particles’ speed before and after tearing through the material. The difference in velocity gave them a direct measurement of the material’s impact resistance, or the amount of energy it can absorb, which turned out to be a surprisingly tough 40 kilojoules per kilogram. This number is measured in the hydrated state.
“That means that a 5-millimeter steel ball launched at 200 meters per second would be arrested by 13 millimeters of the material,” Veysset says. “It is not as resistant as Kevlar, which would require 1 millimeter, but the material beats Kevlar in many other categories.”
It’s no surprise that the new material isn’t as tough as commercial antiballistic materials. It is, however, significantly sturdier than most other nanofibrous hydrogels such as gelatin and synthetic polymers like PVA. The material is also much stretchier than Kevlar. This combination of stretch and strength suggests that, if their fabrication can be sped up, and more films stacked in bouligand structures, nanofibrous hydrogels may serve as flexible and tough artificial tissues.
“For a hydrogel material to be a load-bearing artificial tissue, both strength and deformability are required,” Lin says. “Our material design could achieve these two properties.”
First, this Cambridge is in Massachusetts, US. The US festival was started in 2007 by John Durant, Director of the Massachusetts Institute of Technology (MIT) Museum (see the MIT Museum Wikipedia entry for more information).
The Cambridge Science Festival, the first of its kind in the United States, is a celebration showcasing the leading edge in science, technology, engineering, art, and math (STEAM). A multifaceted, multicultural event, the Festival makes science accessible, interactive and fun, highlighting the impact of STEAM in all our lives.
For the 2021 Festival, recognizing social distancing will be in place as we begin to emerge from the pandemic, we will celebrate STEAM in our community with an overarching theme of gratitude and appreciation. During the month of April 2021, we will showcase creative digital and virtual entries from our rich STEAM community, and celebrate with public displays of appreciation and gratitude. Stay tuned and get involved!
Modeled on art, music, and movie festivals, the Cambridge Science Festival offers activities, demonstrations, workshops, tours, debates, contests, talks, and behind-the-scene glimpses to illuminate the richness of scientific inquiry and the excitement of discovery.
This year, Cambridge Science Festival is celebrating science for the entire month of April. Join us!
Our challenge to you: 30 Days of Science.
Each day, we’ll share a simple prompt with content and events developed exclusively by the Cambridge Science Festival community. Spend a few minutes a day exploring the offerings, connecting with cool scientists, & learning new things!
Or choose your own adventure! Want to learn about a new native bird each day? Maybe perfect your daily coffee routine with science? Ready to learn about 30 exoplanets?
We want to learn with you. We’re here to keep you accountable & cheer you on. Take the pledge — share your discoveries, fun facts, & new questions with us through #30DaysofScience.
MIT engineers have designed a Velcro-like food sensor, made from an array of silk microneedles, that pierces through plastic packaging to sample food for signs of spoilage and bacterial contamination.
The sensor’s microneedles are molded from a solution of edible proteins found in silk cocoons, and are designed to draw fluid into the back of the sensor, which is printed with two types of specialized ink. One of these “bioinks” changes color when in contact with fluid of a certain pH range, indicating that the food has spoiled; the other turns color when it senses contaminating bacteria such as pathogenic E. coli.
The researchers attached the sensor to a fillet of raw fish that they had injected with a solution contaminated with E. coli. After less than a day, they found that the part of the sensor that was printed with bacteria-sensing bioink turned from blue to red — a clear sign that the fish was contaminated. After a few more hours, the pH-sensitive bioink also changed color, signaling that the fish had also spoiled.
The results, published today in the journal Advanced Functional Materials, are a first step toward developing a new colorimetric sensor that can detect signs of food spoilage and contamination.
Such smart food sensors might help head off outbreaks such as the recent salmonella contamination in onions and peaches. They could also prevent consumers from throwing out food that may be past a printed expiration date, but is in fact still consumable.
“There is a lot of food that’s wasted due to lack of proper labeling, and we’re throwing food away without even knowing if it’s spoiled or not,” says Benedetto Marelli, the Paul M. Cook Career Development Assistant Professor in MIT’s Department of Civil and Environmental Engineering. “People also waste a lot of food after outbreaks, because they’re not sure if the food is actually contaminated or not. A technology like this would give confidence to the end user to not waste food.”
Marelli’s co-authors on the paper are Doyoon Kim, Yunteng Cao, Dhanushkodi Mariappan, Michael S. Bono Jr., and A. John Hart.
Silk and printing
The new food sensor is the product of a collaboration between Marelli, whose lab harnesses the properties of silk to develop new technologies, and Hart, whose group develops new manufacturing processes.
Hart recently developed a high-resolution floxography technique, realizing microscopic patterns that can enable low-cost printed electronics and sensors. Meanwhile, Marelli had developed a silk-based microneedle stamp that penetrates and delivers nutrients to plants. In conversation, the researchers wondered whether their technologies could be paired to produce a printed food sensor that monitors food safety.
“Assessing the health of food by just measuring its surface is often not good enough. At some point, Benedetto mentioned his group’s microneedle work with plants, and we realized that we could combine our expertise to make a more effective sensor,” Hart recalls.
The team looked to create a sensor that could pierce through the surface of many types of food. The design they came up with consisted of an array of microneedles made from silk.
“Silk is completely edible, nontoxic, and can be used as a food ingredient, and it’s mechanically robust enough to penetrate through a large spectrum of tissue types, like meat, peaches, and lettuce,” Marelli says.
A deeper detection
To make the new sensor, Kim first made a solution of silk fibroin, a protein extracted from moth cocoons, and poured the solution into a silicone microneedle mold. After drying, he peeled away the resulting array of microneedles, each measuring about 1.6 millimeters long and 600 microns wide — about one-third the diameter of a spaghetti strand.
The team then developed solutions for two kinds of bioink — color-changing printable polymers that can be mixed with other sensing ingredients. In this case, the researchers mixed into one bioink an antibody that is sensitive to a molecule in E. coli. When the antibody comes in contact with that molecule, it changes shape and physically pushes on the surrounding polymer, which in turn changes the way the bioink absorbs light. In this way, the bioink can change color when it senses contaminating bacteria.
The researchers made a bioink containing antibodies sensitive to E. coli, and a second bioink sensitive to pH levels that are associated with spoilage. They printed the bacteria-sensing bioink on the surface of the microneedle array, in the pattern of the letter “E,” next to which they printed the pH-sensitive bioink, as a “C.” Both letters initially appeared blue in color.
Kim then embedded pores within each microneedle to increase the array’s ability to draw up fluid via capillary action. To test the new sensor, he bought several fillets of raw fish from a local grocery store and injected each fillet with a fluid containing either E. coli, Salmonella, or the fluid without any contaminants. He stuck a sensor into each fillet. Then, he waited.
After about 16 hours, the team observed that the “E” turned from blue to red, only in the fillet contaminated with E. coli, indicating that the sensor accurately detected the bacterial antigens. After several more hours, both the “C” and “E” in all samples turned red, indicating that every fillet had spoiled.
The researchers also found their new sensor indicates contamination and spoilage faster than existing sensors that only detect pathogens on the surface of foods.
“There are many cavities and holes in food where pathogens are embedded, and surface sensors cannot detect these,” Kim says. “So we have to plug in a bit deeper to improve the reliability of the detection. Using this piercing technique, we also don’t have to open a package to inspect food quality.”
The team is looking for ways to speed up the microneedles’ absorption of fluid, as well as the bioinks’ sensing of contaminants. Once the design is optimized, they envision the sensor could be used at various stages along the supply chain, from operators in processing plants, who can use the sensors to monitor products before they are shipped out, to consumers who may choose to apply the sensors on certain foods to make sure they are safe to eat.
This world-class symposium, the sixth event of its kind, will bring together a record number (1000+) of renowned Canadian and international experts from across the nanomedicines field to:
highlight the discoveries and innovations in nanomedicines that are contributing to global progress in acute, chronic and orphan disease treatment and management;
present up-to-date diagnostic and therapeutic nanomedicine approaches to addressing the challenges of COVID-19; and
facilitate discussion among nanomedicine researchers and innovators and UBC and NMIN clinician-scientists, basic researchers, trainees, and research partners.
Since 2014, Vancouver Nanomedicine Day has advanced nanomedicine research, knowledge mobilization and commercialization in Canada by sharing high-impact findings and facilitating interaction—among researchers, postdoctoral fellows, graduate students, and life science and startup biotechnology companies—to catalyze research collaboration.
I have a few observations, First, Robert Langer is a big deal. Here are a few highlights from his Wikipedia entry (Note: Links have been removed),
Robert Samuel Langer, Jr. FREng (born August 29, 1948) is an American chemical engineer, scientist, entrepreneur, inventor and one of the twelve Institute Professors at the Massachusetts Institute of Technology.
Langer holds over 1,350 granted or pending patents. He is one of the world’s most highly cited researchers, having authored nearly 1,500 scientific papers, and has participated in the founding of multiple technology companies.
Langer is the youngest person in history (at 43) to be elected to all three American science academies: the National Academy of Sciences, the National Academy of Engineering and the Institute of Medicine. He was also elected as a charter member of National Academy of Inventors. He was elected as an International Fellow of the Royal Academy of Engineering in 2010.
It’s all about commercializing the research—or is it?
(This second observation is a little more complicated and requires a little context.) The NMIN is one of Canada’s Networks of Centres of Excellence (who thought that name up? …sigh), from the NMIN About page,
The NCEs seem to be firmly fixed on finding pathways to commercialization (from the NCE About page) Note: All is not as it seems,
Canada’s global economic competitiveness [emphasis mine] depends on making new discoveries and transforming them into products, services [emphasis mine] and processes that improve the lives of Canadians. To meet this challenge, the Networks of Centres of Excellence (NCE) offers a suite of programs that mobilize Canada’s best research, development and entrepreneurial [emphasis mine] expertise and focus it on specific issues and strategic areas.
NCE programs meet Canada’s needs to focus a critical mass of research resources on social and economic challenges, commercialize [emphasis mine] and apply more of its homegrown research breakthroughs, increase private-sector R&D, [emphasis mine] and train highly qualified people. As economic [emphasis mine] and social needs change, programs have evolved to address new challenges.
The fund will invest $275 million over the next 5 years beginning in fiscal 2018-19, and $65 million ongoing, to fund international, interdisciplinary, fast-breaking and high-risk research.
NFRF is composed of three streams to support groundbreaking research.
Exploration generates opportunities for Canada to build strength in high-risk, high-reward and interdisciplinary research;
Transformation provides large-scale support for Canada to build strength and leadership in interdisciplinary and transformative research; and
International enhances opportunities for Canadian researchers to participate in research with international partners.
As you can see there’s no reference to commercialization or economic challenges.
Here at last is the second observation, I find it hard to believe that the government of Canada has given up on the idea of commercializing research and increasing the country’s economic competitiveness through research. Certainly, Langer’s virtual appearance at Vancouver Nanomedicine Day 2020, suggests that at least some corners of the Canadian research establishment are remaining staunchly entrepreneurial.
Canada remains strong in research output and impact, capacity for R&D and innovation at risk: New expert panel report
While Canada is a highly innovative country, with a robust research base and thriving communities of technology start-ups, significant barriers—such as a lack of managerial skills, the experience needed to scale-up companies, and foreign acquisition of high-tech firms—often prevent the translation of innovation into wealth creation.[emphasis mine] The result is a deficit of technology companies growing to scale in Canada, and a loss of associated economic and social benefits.This risks establishing a vicious cycle, where successful companies seek growth opportunities elsewhere due to a lack of critical skills and experience in Canada guiding companies through periods of rapid expansion.
According to the CCA’s [2018 report] Summary webpage, it was Innovation, Science and Economic Development Canada which requested the report. (I wrote up a two-part commentary under one of my favourite titles: “The Hedy Lamarr of international research: Canada’s Third assessment of The State of Science and Technology and Industrial Research and Development in Canada.” Part 1 and Part 2)
I will be fascinated to watch the NFRF and science commercialization situations as they develop.
This is the second neuromorphic computing chip story from MIT this summer in what has turned out to be a bumper crop of research announcements in this field. The first MIT synapse story was featured in a June 16, 2020 posting. Now, there’s a second and completely different team announcing results for their artificial brain synapse work in a June 19, 2020 news item on Nanowerk (Note: A link has been removed),
Teams around the world are building ever more sophisticated artificial intelligence systems of a type called neural networks, designed in some ways to mimic the wiring of the brain, for carrying out tasks such as computer vision and natural language processing.
Using state-of-the-art semiconductor circuits to simulate neural networks requires large amounts of memory and high power consumption. Now, an MIT [Massachusetts Institute of Technology] team has made strides toward an alternative system, which uses physical, analog devices that can much more efficiently mimic brain processes.
The findings are described in the journal Nature Communications (“Protonic solid-state electrochemical synapse for physical neural networks”), in a paper by MIT professors Bilge Yildiz, Ju Li, and Jesús del Alamo, and nine others at MIT and Brookhaven National Laboratory. The first author of the paper is Xiahui Yao, a former MIT postdoc now working on energy storage at GRU Energy Lab.
That description of the work is one pretty much every team working on developing memristive (neuromorphic) chips could use.
On other fronts, the team has produced a very attractive illustration accompanying this research (aside: Is it my imagination or has there been a serious investment in the colour pink and other pastels for science illustrations?),
A June 19, 2020 MIT news release, which originated the news item, provides more insight into this specific piece of research (hint: it’s about energy use and repeatability),
Neural networks attempt to simulate the way learning takes place in the brain, which is based on the gradual strengthening or weakening of the connections between neurons, known as synapses. The core component of this physical neural network is the resistive switch, whose electronic conductance can be controlled electrically. This control, or modulation, emulates the strengthening and weakening of synapses in the brain.
In neural networks using conventional silicon microchip technology, the simulation of these synapses is a very energy-intensive process. To improve efficiency and enable more ambitious neural network goals, researchers in recent years have been exploring a number of physical devices that could more directly mimic the way synapses gradually strengthen and weaken during learning and forgetting.
Most candidate analog resistive devices so far for such simulated synapses have either been very inefficient, in terms of energy use, or performed inconsistently from one device to another or one cycle to the next. The new system, the researchers say, overcomes both of these challenges. “We’re addressing not only the energy challenge, but also the repeatability-related challenge that is pervasive in some of the existing concepts out there,” says Yildiz, who is a professor of nuclear science and engineering and of materials science and engineering.
“I think the bottleneck today for building [neural network] applications is energy efficiency. It just takes too much energy to train these systems, particularly for applications on the edge, like autonomous cars,” says del Alamo, who is the Donner Professor in the Department of Electrical Engineering and Computer Science. Many such demanding applications are simply not feasible with today’s technology, he adds.
The resistive switch in this work is an electrochemical device, which is made of tungsten trioxide (WO3) and works in a way similar to the charging and discharging of batteries. Ions, in this case protons, can migrate into or out of the crystalline lattice of the material, explains Yildiz, depending on the polarity and strength of an applied voltage. These changes remain in place until altered by a reverse applied voltage — just as the strengthening or weakening of synapses does.
The mechanism is similar to the doping of semiconductors,” says Li, who is also a professor of nuclear science and engineering and of materials science and engineering. In that process, the conductivity of silicon can be changed by many orders of magnitude by introducing foreign ions into the silicon lattice. “Traditionally those ions were implanted at the factory,” he says, but with the new device, the ions are pumped in and out of the lattice in a dynamic, ongoing process. The researchers can control how much of the “dopant” ions go in or out by controlling the voltage, and “we’ve demonstrated a very good repeatability and energy efficiency,” he says.
Yildiz adds that this process is “very similar to how the synapses of the biological brain work. There, we’re not working with protons, but with other ions such as calcium, potassium, magnesium, etc., and by moving those ions you actually change the resistance of the synapses, and that is an element of learning.” The process taking place in the tungsten trioxide in their device is similar to the resistance modulation taking place in biological synapses, she says.
“What we have demonstrated here,” Yildiz says, “even though it’s not an optimized device, gets to the order of energy consumption per unit area per unit change in conductance that’s close to that in the brain.” Trying to accomplish the same task with conventional CMOS type semiconductors would take a million times more energy, she says.
The materials used in the demonstration of the new device were chosen for their compatibility with present semiconductor manufacturing systems, according to Li. But they include a polymer material that limits the device’s tolerance for heat, so the team is still searching for other variations of the device’s proton-conducting membrane and better ways of encapsulating its hydrogen source for long-term operations.
“There’s a lot of fundamental research to be done at the materials level for this device,” Yildiz says. Ongoing research will include “work on how to integrate these devices with existing CMOS transistors” adds del Alamo. “All that takes time,” he says, “and it presents tremendous opportunities for innovation, great opportunities for our students to launch their careers.”
Coincidentally or not a University of Massachusetts at Amherst team announced memristor voltage use comparable to human brain voltage use (see my June 15, 2020 posting), plus, there’s a team at Stanford University touting their low-energy biohybrid synapse in a XXX posting. (June 2020 has been a particularly busy month here for ‘artificial brain’ or ‘memristor’ stories.)
Getting back to this latest MIT research, here’s a link to and a citation for the paper,
Protonic solid-state electrochemical synapse for physical neural networks by Xiahui Yao, Konstantin Klyukin, Wenjie Lu, Murat Onen, Seungchan Ryu, Dongha Kim, Nicolas Emond, Iradwikanari Waluyo, Adrian Hunt, Jesús A. del Alamo, Ju Li & Bilge Yildiz. Nature Communications volume 11, Article number: 3134 (2020) DOI: https://doi.org/10.1038/s41467-020-16866-6 Published: 19 June 2020
Clustered regularly interspersed short palindromic repeats (CRISPR) gene editing has been largely confined to laboratory use or tested in agricultural trials. I believe that is true worldwide excepting the CRISPR twin scandal. (There are numerous postings about the CRISPR twins here including a Nov. 28, 2018 post, a May 17, 2019 post, and a June 20, 2019 post. Update: It was reported (3rd. para.) in December 2019 that He had been sentenced to three years jail time.)
Connie Lin in a May 7, 2020 article for Fast Company reports on this surprising decision by the US Food and Drug Administration (FDA), Note: A link has been removed),
The U.S. Food and Drug Administration has granted Emergency Use Authorization to a COVID-19 test that uses controversial gene-editing technology CRISPR.
This marks the first time CRISPR has been authorized by the FDA, although only for the purpose of detecting the coronavirus, and not for its far more contentious applications. The new test kit, developed by Cambridge, Massachusetts-based Sherlock Biosciences, will be deployed in laboratories certified to carry out high-complexity procedures and is “rapid,” returning results in about an hour as opposed to those that rely on the standard polymerase chain reaction method, which typically requires six hours.
The announcement was made in the FDA’s Coronavirus (COVID-19) Update: May 7, 2020 Daily Roundup (4th item in the bulleted list), Or, you can read the May 6, 2020 letter (PDF) sent to John Vozella of Sherlock Biosciences by the FDA.
Sherlock Biosciences, an Engineering Biology company dedicated to making diagnostic testing better, faster and more affordable, today announced the company has received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA) for its Sherlock™ CRISPR SARS-CoV-2 kit for the detection of the virus that causes COVID-19, providing results in approximately one hour.
“While it has only been a little over a year since the launch of Sherlock Biosciences, today we have made history with the very first FDA-authorized use of CRISPR technology, which will be used to rapidly identify the virus that causes COVID-19,” said Rahul Dhanda, co-founder, president and CEO of Sherlock Biosciences. “We are committed to providing this initial wave of testing kits to physicians, laboratory experts and researchers worldwide to enable them to assist frontline workers leading the charge against this pandemic.”
The Sherlock™ CRISPR SARS-CoV-2 test kit is designed for use in laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, to perform high complexity tests. Based on the SHERLOCK method, which stands for Specific High-sensitivity Enzymatic Reporter unLOCKing, the kit works by programming a CRISPR molecule to detect the presence of a specific genetic signature – in this case, the genetic signature for SARS-CoV-2 – in a nasal swab, nasopharyngeal swab, oropharyngeal swab or bronchoalveolar lavage (BAL) specimen. When the signature is found, the CRISPR enzyme is activated and releases a detectable signal. In addition to SHERLOCK, the company is also developing its INSPECTR™ platform to create an instrument-free, handheld test – similar to that of an at-home pregnancy test – that utilizes Sherlock Biosciences’ Synthetic Biology platform to provide rapid detection of a genetic match of the SARS-CoV-2 virus.
“When our lab collaborated with Dr. Feng Zhang’s team to develop SHERLOCK, we believed that this CRISPR-based diagnostic method would have a significant impact on global health,” said James J. Collins, co-founder and board member of Sherlock Biosciences and Termeer Professor of Medical Engineering and Science for MIT’s Institute for Medical Engineering and Science (IMES) and Department of Biological Engineering. “During what is a major healthcare crisis across the globe, we are heartened that the first FDA-authorized use of CRISPR will aid in the fight against this global COVID-19 pandemic.”
Access to rapid diagnostics is critical for combating this pandemic and is a primary focus for Sherlock Biosciences co-founder and board member, David R. Walt, Ph.D., who co-leads the Mass [Massachusetts] General Brigham Center for COVID Innovation.
“SHERLOCK enables rapid identification of a single alteration in a DNA or RNA sequence in a single molecule,” said Dr. Walt. “That precision, coupled with its capability to be deployed to multiplex over 100 targets or as a simple point-of-care system, will make it a critical addition to the arsenal of rapid diagnostics already being used to detect COVID-19.”
This development is particularly interesting since there was a major intellectual property dispute over CRISPR between the Broad Institute (a Harvard University and Massachusetts Institute of Technology [MIT] joint initiative), and the University of California at Berkeley (UC Berkeley). The Broad Institute mostly won in the first round of the patent fight, as I noted in a March 15, 2017 post but, as far as I’m aware, UC Berkeley is still disputing that decision.
In the period before receiving authorization, it appears that Sherlock Biosciences was doing a little public relations and ‘consciousness raising’ work. Here’s a sample from a May 5, 2020 article by Sharon Begley for STAT (Note: Links have been removed),
The revolutionary genetic technique better known for its potential to cure thousands of inherited diseases could also solve the challenge of Covid-19 diagnostic testing, scientists announced on Tuesday. A team headed by biologist Feng Zhang of the McGovern Institute at MIT and the Broad Institute has repurposed the genome-editing tool CRISPR into a test able to quickly detect as few as 100 coronavirus particles in a swab or saliva sample.
Crucially, the technique, dubbed a “one pot” protocol, works in a single test tube and does not require the many specialty chemicals, or reagents, whose shortage has hampered the rollout of widespread Covid-19 testing in the U.S. It takes about an hour to get results, requires minimal handling, and in preliminary studies has been highly accurate, Zhang told STAT. He and his colleagues, led by the McGovern’s Jonathan Gootenberg and Omar Abudayyeh, released the protocol on their STOPCovid.science website.
Because the test has not been approved by the Food and Drug Administration, it is only for research purposes for now. But minutes before speaking to STAT on Monday, Zhang and his colleagues were on a conference call with FDA officials about what they needed to do to receive an “emergency use authorization” that would allow clinical use of the test. The FDA has used EUAs to fast-track Covid-19 diagnostics as well as experimental therapies, including remdesivir, after less extensive testing than usually required.
For an EUA, the agency will require the scientists to validate the test, which they call STOPCovid, on dozens to hundreds of samples. Although “it is still early in the process,” Zhang said, he and his colleagues are confident enough in its accuracy that they are conferring with potential commercial partners who could turn the test into a cartridge-like device, similar to a pregnancy test, enabling Covid-19 testing at doctor offices and other point-of-care sites.
“It could potentially even be used at home or at workplaces,” Zhang said. “It’s inexpensive, does not require a lab, and can return results within an hour using a paper strip, not unlike a pregnancy test. This helps address the urgent need for widespread, accurate, inexpensive, and accessible Covid-19 testing.” Public health experts say the availability of such a test is one of the keys to safely reopening society, which will require widespread testing, and then tracing and possibly isolating the contacts of those who test positive.
There’s a very good November 11, 2019 article by Natalie Angier for the New York Times on carbon nanotubes (CNTs) and the colour black,
On a laboratory bench at the National Institute of Standards and Technology was a square tray with two black disks inside, each about the width of the top of a Dixie cup. Both disks were undeniably black, yet they didn’t look quite the same.
Solomon Woods, 49, a trim, dark-haired, soft-spoken physicist, was about to demonstrate how different they were, and how serenely voracious a black could be.
“The human eye is extraordinarily sensitive to light,” Dr. Woods said. Throw a few dozen photons its way, a few dozen quantum-sized packets of light, and the eye can readily track them.
Dr. Woods pulled a laser pointer from his pocket. “This pointer,” he said, “puts out 100 trillion photons per second.” He switched on the laser and began slowly sweeping its bright beam across the surface of the tray.
On hitting the white background, the light bounced back almost unimpeded, as rude as a glaring headlight in a rearview mirror.
The beam moved to the first black disk, a rondel of engineered carbon now more than a decade old. The light dimmed significantly, as a sizable tranche of the incident photons were absorbed by the black pigment, yet the glow remained surprisingly strong.
Finally Dr. Woods trained his pointer on the second black disk, and suddenly the laser’s brilliant beam, its brash photonic probe, simply — disappeared. Trillions of light particles were striking the black disk, and virtually none were winking back up again. It was like watching a circus performer swallow a sword, or a husband “share” your plate of French fries: Hey, where did it all go?
N.I.S.T. disk number two was an example of advanced ultra-black technology: elaborately engineered arrays of tiny carbon cylinders, or nanotubes, designed to capture and muzzle any light they encounter. Blacker is the new black, and researchers here and abroad are working to create ever more efficient light traps, which means fabricating materials that look ever darker, ever flatter, ever more ripped from the void.
The N.I.S.T. ultra-black absorbs at least 99.99 percent of the light that stumbles into its nanotube forest. But scientists at the Massachusetts Institute of Technology reported in September the creation of a carbon nanotube coating that they claim captures better than 99.995 of the incident light.
… The more fastidious and reliable the ultra-black, the more broadly useful it will prove to be — in solar power generators, radiometers, industrial baffles and telescopes primed to detect the faintest light fluxes as a distant planet traverses the face of its star.
Psychology and metaphors
It’s not all technical, Angier goes on to mention the psychological and metaphorical aspects,
Psychologists have gathered evidence that black is among the most metaphorically loaded of all colors, and that we absorb our often contradictory impressions about black at a young age.
Reporting earlier this year in the Quarterly Journal of Experimental Psychology, Robin Kramer and Joanne Prior of the University of Lincoln in the United Kingdom compared color associations in a group of 104 children, aged 5 to 10, with those of 100 university students.
The researchers showed subjects drawings in which a lineup of six otherwise identical images differed only in some aspect of color. The T-shirt of a boy taking a test, for example, was switched from black to blue to green to red to white to yellow. The same for a businessman’s necktie, a schoolgirl’s dress, a dog’s collar, a boxer’s gloves.
Participants were asked to link images with traits. Which boy was likeliest to cheat on the test? Which man was likely to be in charge at work? Which girl was the smartest in her class, which dog the scariest?
Again and again, among both children and young adults, black pulled ahead of nearly every color but red. Black was the color of cheating, and black was the color of cleverness. A black tie was the mark of a boss, a black collar the sign of a pit bull. Black was the color of strength and of winning. Black was the color of rage.
Then, there is the world of art,
For artists, black is basal and nonnegotiable, the source of shadow, line, volume, perspective and mood. “There is a black which is old and a black which is fresh,” Ad Reinhardt, the abstract expressionist artist, said. “Lustrous black and dull black, black in sunlight and black in shadow.”
So essential is black to any aesthetic act that, as David Scott Kastan and Stephen Farthing describe in their scholarly yet highly entertaining book, “On Color,” modern artists have long squabbled over who pioneered the ultimate visual distillation: the all-black painting.
Was it the Russian Constructivist Aleksandr Rodchenko, who in 1918 created a series of eight seemingly all-black canvases? No, insisted the American artist Barnett Newman: Those works were very dark brown, not black. He, Mr. Newman, deserved credit for his 1949 opus, “Abraham,” which in 1966 he described as “the first and still the only black painting in history.”
But what about Kazimir Malevich’s “Black Square” of 1915? True, it was a black square against a white background, but the black part was the point. Then again, the English polymath Robert Fludd had engraved a black square in a white border back in 1617.
Clearly, said Alfred H. Barr, Jr., the first director of the Museum of Modern Art, “Each generation must paint its own black square.”
Solomon and his NIST colleagues and the MIT scientists are all trying to create materials with structural colour, in this case, black. Angier goes on to discuss structural colour in nature mentioning bird feathers and spiders as examples of where you might find superblacks. For anyone unfamiliar with structural colour, the colour is not achieved with pigment or dye but with tiny structures, usually measured at the nanoscale, on a bird’s wing, a spider’s belly, a plant leaf, etc. Structural colour does not fade or change . Still, it’s possible to destroy the structures, i.e., the colour, but light and time will not have any effect since it’s the tiny structures and their optical properties which are producing the colour . (Even after all these years, my favourite structural colour story remains a Feb. 1, 2013 article, Color from Structure, by Cristina Luiggi for The Scientist magazine. For a shorter version, I excerpted parts of Luiggi’s story for my February 7, 2013 posting.)
The examples of structural colour in Angier’s article were new to me. However, there are many, many examples elsewhere,. You can find some here by using the terms ‘structural colour’ or ‘structural color’ in the blog’s search engine.
Angier’s is a really good article and I strongly recommend reading it if you have time but I’m a little surprised she doesn’t mention Vantablack and the artistic feud. More about that in a moment,
Massachusetts Institute of Technology and a ‘blacker black’
According to MIT (Massachusetts Institute of Technology), they have the blackest black. It too is courtesy of carbon nanotubes.
What you see in the above ‘The Redemption of Vanity’ was on show at the New York Stock Exchange (NYSE) from September 13 – November 29, 2019. It’s both an art piece and a demonstration of MIT’s blackest black.
With apologies to “Spinal Tap,” it appears that black can, indeed, get more black.
MIT engineers report today that they have cooked up a material that is 10 times blacker than anything that has previously been reported. The material is made from vertically aligned carbon nanotubes, or CNTs — microscopic filaments of carbon, like a fuzzy forest of tiny trees, that the team grew on a surface of chlorine-etched aluminum foil. The foil captures at least 99.995 percent* of any incoming light, making it the blackest material on record.
The researchers have published their findings today in the journal ACS-Applied Materials and Interfaces. They are also showcasing the cloak-like material as part of a new exhibit today at the New York Stock Exchange, titled “The Redemption of Vanity.”
The artwork, conceived by Diemut Strebe, an artist-in-residence at the MIT Center for Art, Science, and Technology, in collaboration with Brian Wardle, professor of aeronautics and astronautics at MIT, and his group, and MIT Center for Art, Science, and Technology artist-in-residence Diemut Strebe, features a 16.78-carat natural yellow diamond from LJ West Diamonds, estimated to be worth $2 million, which the team coated with the new, ultrablack CNT material. The effect is arresting: The gem, normally brilliantly faceted, appears as a flat, black void.
Wardle says the CNT material, aside from making an artistic statement, may also be of practical use, for instance in optical blinders that reduce unwanted glare, to help space telescopes spot orbiting exoplanets.
“There are optical and space science applications for very black materials, and of course, artists have been interested in black, going back well before the Renaissance,” Wardle says. “Our material is 10 times blacker than anything that’s ever been reported, but I think the blackest black is a constantly moving target. Someone will find a blacker material, and eventually we’ll understand all the underlying mechanisms, and will be able to properly engineer the ultimate black.”
Wardle’s co-author on the paper is former MIT postdoc Kehang Cui, now a professor at Shanghai Jiao Tong University.
Into the void
Wardle and Cui didn’t intend to engineer an ultrablack material. Instead, they were experimenting with ways to grow carbon nanotubes on electrically conducting materials such as aluminum, to boost their electrical and thermal properties.
But in attempting to grow CNTs on aluminum, Cui ran up against a barrier, literally: an ever-present layer of oxide that coats aluminum when it is exposed to air. This oxide layer acts as an insulator, blocking rather than conducting electricity and heat. As he cast about for ways to remove aluminum’s oxide layer, Cui found a solution in salt, or sodium chloride.
At the time, Wardle’s group was using salt and other pantry products, such as baking soda and detergent, to grow carbon nanotubes. In their tests with salt, Cui noticed that chloride ions were eating away at aluminum’s surface and dissolving its oxide layer.
“This etching process is common for many metals,” Cui says. “For instance, ships suffer from corrosion of chlorine-based ocean water. Now we’re using this process to our advantage.”
Cui found that if he soaked aluminum foil in saltwater, he could remove the oxide layer. He then transferred the foil to an oxygen-free environment to prevent reoxidation, and finally, placed the etched aluminum in an oven, where the group carried out techniques to grow carbon nanotubes via a process called chemical vapor deposition.
By removing the oxide layer, the researchers were able to grow carbon nanotubes on aluminum, at much lower temperatures than they otherwise would, by about 100 degrees Celsius. They also saw that the combination of CNTs on aluminum significantly enhanced the material’s thermal and electrical properties — a finding that they expected.
What surprised them was the material’s color.
“I remember noticing how black it was before growing carbon nanotubes on it, and then after growth, it looked even darker,” Cui recalls. “So I thought I should measure the optical reflectance of the sample.
“Our group does not usually focus on optical properties of materials, but this work was going on at the same time as our art-science collaborations with Diemut, so art influenced science in this case,” says Wardle.
Wardle and Cui, who have applied for a patent on the technology, are making the new CNT process freely available to any artist to use for a noncommercial art project.
“Built to take abuse”
Cui measured the amount of light reflected by the material, not just from directly overhead, but also from every other possible angle. The results showed that the material absorbed at least 99.995 percent of incoming light, from every angle. In other words, it reflected 10 times less light than all other superblack materials, including Vantablack. If the material contained bumps or ridges, or features of any kind, no matter what angle it was viewed from, these features would be invisible, obscured in a void of black.
The researchers aren’t entirely sure of the mechanism contributing to the material’s opacity, but they suspect that it may have something to do with the combination of etched aluminum, which is somewhat blackened, with the carbon nanotubes. Scientists believe that forests of carbon nanotubes can trap and convert most incoming light to heat, reflecting very little of it back out as light, thereby giving CNTs a particularly black shade.
“CNT forests of different varieties are known to be extremely black, but there is a lack of mechanistic understanding as to why this material is the blackest. That needs further study,” Wardle says.
The material is already gaining interest in the aerospace community. Astrophysicist and Nobel laureate John Mather, who was not involved in the research, is exploring the possibility of using Wardle’s material as the basis for a star shade — a massive black shade that would shield a space telescope from stray light.
“Optical instruments like cameras and telescopes have to get rid of unwanted glare, so you can see what you want to see,” Mather says. “Would you like to see an Earth orbiting another star? We need something very black. … And this black has to be tough to withstand a rocket launch. Old versions were fragile forests of fur, but these are more like pot scrubbers — built to take abuse.”
[Note] An earlier version of this story stated that the new material captures more than 99.96 percent of incoming light. That number has been updated to be more precise; the material absorbs at least 99.995 of incoming light.
Here’s an August 29, 2019 news release from MIT announcing the then upcoming show. Usually I’d expect to see a research paper associated with this work but this time it seems to an art exhibit only,
The MIT Center for Art, Science &Technology (CAST) and the New York Stock Exchange (NYSE) will present The Redemption of Vanity,created by artist Diemut Strebe in collaboration with MIT scientist Brian Wardle and his lab, on view at the New York Stock Exchange September 13, 2019 -November 25, 2019. For the work, a 16.78 carat natural yellow diamond valued at $2 million from L.J.West was coated using a new procedure of generating carbon nanotubes (CNTs), recently measured to be the blackest black ever created, which makes the diamond seem to disappear into an invisible void. The patented carbon nanotube technology (CNT) absorbs more than 99.96% of light and was developed by Professor Wardle and his necstlablab at MIT.
“Any object covered with this CNT material loses all its plasticity and appears entirely flat, abbreviated/reduced to a black silhouette. In outright contradiction to this we see that a diamond,while made of the very same element (carbon) performs the most intense reflection of light on earth.Because of the extremely high light absorbtive qualities of the CNTs, any object, in this case a large diamond coated with CNT’s, becomes a kind of black hole absent of shadows,“ explains Strebe.“The unification of extreme opposites in one object and the particular aesthetic features of the CNTs caught my imagination for this art project.”
“Strebe’s art-science collaboration caused us to look at the optical properties of our new CNT growth, and we discovered that these particular CNTs are blacker than all other reported materials by an order of magnitude across the visible spectrum”, says Wardle. The MIT team is offering the process for any artist to use. “We do not believe in exclusive ownership of any material or idea for any artwork and have opened our method to any artist,” say Strebe and Wardle.“
The project explores material and immaterial value attached to objects and concepts in reference to luxury, society and to art. We are presenting the literal devaluation of a diamond, which is highly symbolic and of high economic value.It presents a challenge to art market mechanisms on the one hand, while expressing at the same time questions of the value of art in a broader way. In this sense it manifests an inquiry into the significance of the value of objects of art and the art market,” says Strebe. “We are honored to present this work at The New York Stock Exchange, which I believe to be a most fitting location to consider the ideas embedded in The Redemption of Vanity.”
“The New York Stock Exchange, a center of financial and technological innovation for 227 years, is the perfect venue to display Diemut Strebe and Professor Brian Wardle’s collaboration. Their work brings together cutting-edge nanotube technology and a natural diamond, which is a symbol of both value and longevity,” said John Tuttle, NYSE Group Vice Chairman & Chief Commercial Officer.
“We welcome all scientists and artists to venture into the world of natural color diamonds. The Redemption of Vanity exemplifies the bond between art, science, and luxury. The 16-carat vivid yellow diamond in the exhibit spent millions of years in complete darkness, deep below the earth’s surface. It was only recently unearthed —a once-in-a-lifetime discovery of exquisite size and color. Now the diamond will relive its journey to darkness as it is covered in the blackest of materials. Once again, it will become a reminder that something rare and beautiful can exist even in darkness,”said Larry West.
The “disappearing” diamond in The Redemption of Vanity is a $2 Million Fancy Vivid Yellow SI1 (GIA), Radiant shape, from color diamond specialist, L.J. West Diamonds Inc. of New York.
The Redemption of Vanity, conceived by Diemut Strebe, has been realized with Brian L. Wardle, Professor of Aeronautics and Astronautics and Director of necstlab and Nano-Engineered Composite aerospace STructures (NECST) Consortium and his team Drs. Luiz Acauan and Estelle Cohen, in conjunction with Strebe’s residency at MIT supported by the Center for Art, Science & Technology (CAST).
ABOUT THE ARTISTS
Diemut Strebe is a conceptual artist based in Boston, MA and a MIT CAST Visiting Artist. She has collaborated with several MIT faculty, including Noam Chomsky and Robert Langer on Sugababe (2014), Litmus (2014) and Yeast Expression(2015); Seth Lloyd and Dirk Englund on Wigner’s Friends(2014); Alan Guth on Plötzlich! (2018); researchers in William Tisdale’s Lab on The Origin of the Works of Art(2018); Regina Barzilay and Elchanan Mossel on The Prayer (2019); and Ken Kamrin and John Brisson on The Gymnast (2019). Strebe is represented by the Ronald Feldman Gallery.
Brian L. Wardle is a Professor of Aeronautics and Astronautics at MIT and the director of the necstlab research group and MIT’s Nano-Engineered Composite aerospace STructures (NECST) Consortium. Wardle previously worked with CAST Visiting Artist Trevor Paglen on The Last Picturesproject (2012).
ABOUT THE MIT CENTER FOR ART, SCIENCE & TECHNOLOGY
A major cross-school initiative, the MIT Center for Art, Science & Technology (CAST) creates new opportunities for art, science and technology to thrive as interrelated, mutually informing modes of exploration, knowledge and discovery. CAST’s multidisciplinary platform presents performing and visual arts programs, supports research projects for artists working with science and engineering labs, and sponsors symposia, classes, workshops, design studios, lectures and publications. The Center is funded in part by a generous grant from the Andrew W. Mellon Foundation. Evan Ziporyn is the Faculty Director and Leila W. Kinney is the Executive Director.Since its inception in 2012, CAST has been the catalyst for more than 150 artist residencies and collaborative projects with MIT faculty and students, including numerous cross-disciplinary courses, workshops, concert series, multimedia projects, lectures and symposia. The visiting artists program is a cornerstone of CAST’s activities, which encourages cross-fertilization among disciplines and intensive interaction with MIT’s faculty and students. More info at https://arts.mit.edu/cast/ .
HISTORY OF VISITING ARTISTS AT MIT
Since the late 1960s, MIT has been a leader in integrating the arts and pioneering a model for collaboration among artists, scientists and engineers in a research setting. CAST’s Visiting Artists Program brings internationally acclaimed artists to engage with MIT’s creative community in ways that are mutually enlightening for the artists and for faculty, students and research staff at the Institute. Artists who have worked extensively at MIT include Mel Chin, Olafur Eliasson, Rick Lowe, Vik Muniz, Trevor Paglen, Tomás Saraceno, Maya Beiser, Agnieszka Kurant, and Anicka Yi.
ABOUT L.J. WEST DIAMONDS
L.J. West Diamonds is a three generation natural color diamond whole sale rfounded in the late 1970’s by Larry J. West and based in New York City. L.J. West has established itself as one of the world’s prominent houses for some of the most rare and important exotic natural fancy color diamonds to have ever been unearthed. This collection includes a vast color spectrum of rare pink, blue, yellow, green, orange and red diamonds. L.J. West is an expert in every phase of the jewelry process –from sourcing to the cutting, polishing and final design. Each exceptional jewel is carefully set to become a unique work of art.The Redemption of Vanity is on view at the New York Stock Exchange by appointment only.
Press viewing: September 13, 2019 at 3pmNew York Stock Exchange, 11 Wall Street, New York, NY 10005RSVP required. Please check-in at the blue tent at 2 Broad Street(at the corner of Wall and Broad Streets). All guests are required to show a government issued photo ID and go through airport-like security upon entering the NYSE.NYSE follows a business casual dress code -jeans & sneakers are not permitted.
No word yet if there will be other showings.
An artistic feud (of sorts)
Earlier this year, I updated a story on Vantablack. It was the blackest black, blocking 99.8% of light when I featured it in a March 14, 2016 posting. The UK company making the announcement, Surrey NanoSystems, then laid the groundwork for an artistic feud when it granted exclusive rights to their carbon nanotube-based coating, Vantablack, to Sir Anish Kapoor mentioned here in an April 16, 2016 posting.
This exclusivity outraged some artists notably, Stuart Semple. In his first act of defiance, he created the pinkest pink. Next, came a Kickstarter campaign to fund Semple’s blackest black, which would be available to all artists except Anish Kapoor. You can read all about the pinkest pink and blackest black as per Semple in my February 21, 2019 posting. You can also get a bit of an update in an Oct. 17, 2019 Stuart Semple proffile by Berenice Baker for Verdict,
… so I managed to hire a scientist, Jemima, to work in the studio with me. She got really close to a super black, and we made our own pigment to this recipe and it was awesome, but we couldn’t afford to put it into manufacture because it cost £25,000.”
Semple launched a Kickstarter campaign and was amazed to raise half a million pounds, making it the second most-supported art Kickstarter of all time.
The ‘race to the blackest’ is well underway, with MIT researchers recently announcing a carbon nanotube-based black whose light absorption they tested by coasting a diamond. But Semple is determined that his black should be affordable by all artists and work like a paint, not only perform in laboratory conditions. He’s currently working with Jemima and two chemists to upgrade the recipe for Black 3.2.
I don’t know how Semple arrived at his blackest black. I think it’s unlikely that he achieved the result by working with carbon nanotubes since my understanding is that CNTs aren’t that easy to produce.
Interesting, eh? In just a few years scientists have progressed from achieving a 99.8% black to 99.999%. It doesn’t seem like that big a difference to me but with Solomon Woods, at the beginning of this post, making the point that our eyes are very sensitive to light, an artistic feud, and a study uncovering deep emotions, getting the blackest black is a much more artistically fraught endeavour than I had imagined.
The latest camelid-oriented medical research story is in an April 11, 2019 news item on phys.org (Note: A link has been removed),
In 1989, two undergraduate students at the Free University of Brussels were asked to test frozen blood serum from camels, and stumbled on a previously unknown kind of antibody. It was a miniaturized version of a human antibody, made up only of two heavy protein chains, rather than two light and two heavy chains. As they eventually reported, the antibodies’ presence was confirmed not only in camels, but also in llamas and alpacas.
Fast forward 30 years. In the journal PNAS [Proceedings of the National Academy of Science] this week [April 8 – 12, 2019], researchers at Boston Children’s Hospital and MIT [Massachusetts Institute of Technology] show that these mini-antibodies, shrunk further to create so-called nanobodies, may help solve a problem in the cancer field: making CAR T-cell therapies work in solid tumors.
Highly promising for blood cancers, chimeric antigen receptor (CAR) T-cell therapy genetically engineers a patient’s own T cells to make them better at attacking cancer cells. The Dana-Farber/Boston Children’s Cancer and Blood Disorders Center is currently using CAR T-cell therapy for relapsed acute lymphocytic leukemia (ALL), for example.
But CAR T cells haven’t been good at eliminating solid tumors. It’s been hard to find cancer-specific proteins on solid tumors that could serve as safe targets. Solid tumors are also protected by an extracellular matrix, a supportive web of proteins that acts as a barrier, as well as immunosuppressive molecules that weaken the T-cell attack.
Rethinking CAR T cells
That’s where nanobodies come in. For two decades, they largely remained in the hands of the Belgian team. But that changed after the patent expired in 2013. [emphases mine]
“A lot of people got into the game and began to appreciate nanobodies’ unique properties,” says Hidde Ploegh, PhD, an immunologist in the Program in Cellular and Molecular Medicine at Boston Children’s and senior investigator on the PNAS study.
One useful attribute is their enhanced targeting abilities. Ploegh and his team at Boston Children’s, in collaboration with Noo Jalikhani, PhD, and Richard Hynes, PhD at MIT’s Koch Institute for Integrative Cancer Research, have harnessed nanobodies to carry imaging agents, allowing precise visualization of metastatic cancers.
The Hynes team targeted the nanobodies to the tumors’ extracellular matrix, or ECM — aiming imaging agents not at the cancer cells themselves, but at the environment that surrounds them. Such markers are common to many tumors, but don’t typically appear on normal cells.
“Our lab and the Hynes lab are among the few actively pursuing this approach of targeting the tumor micro-environment,” says Ploegh. “Most labs are looking for tumor-specific antigens.”
Targeting tumor protectors
Ploegh’s lab took this idea to CAR T-cell therapy. His team, including members of the Hynes lab, took aim at the very factors that make solid tumors difficult to treat.
The CAR T cells they created were studded with nanobodies that recognize specific proteins in the tumor environment, bearing signals directing them to kill any cell they bound to. One protein, EIIIB, a variant of fibronectin, is found only on newly formed blood vessels that supply tumors with nutrients. Another, PD-L1, is an immunosuppressive protein that most cancers use to silence approaching T cells.
Biochemist Jessica Ingram, PhD of the Dana-Farber Cancer Institute, Ploegh’s partner and a coauthor on the paper, led the manufacturing pipeline. She would drive to Amherst, Mass., to gather T cells from two alpacas, Bryson and Sanchez, inject them with the antigen of interest and harvest their blood for further processing back in Boston to generate mini-antibodies.
Taking down melanoma and colon cancer
Tested in two separate melanoma mouse models, as well as a colon adenocarcinoma model in mice, the nanobody-based CAR T cells killed tumor cells, significantly slowed tumor growth and improved the animals’ survival, with no readily apparent side effects.
Ploegh thinks that the engineered T cells work through a combination of factors. They caused damage to tumor tissue, which tends to stimulate inflammatory immune responses. Targeting EIIIB may damage blood vessels in a way that decreases blood supply to tumors, while making them more permeable to cancer drugs.
“If you destroy the local blood supply and cause vascular leakage, you could perhaps improve the delivery of other things that might have a harder time getting in,” says Ploegh. “I think we should look at this as part of a combination therapy.”
Ploegh thinks his team’s approach could be useful in many solid tumors. He’s particularly interested in testing nanobody-based CAR T cells in models of pancreatic cancer and cholangiocarcinoma, a bile duct cancer from which Ingram passed away in 2018.
The technology itself can be pushed even further, says Ploegh.
“Nanobodies could potentially carry a cytokine to boost the immune response to the tumor, toxic molecules that kill tumor and radioisotopes to irradiate the tumor at close range,” he says. “CAR T cells are the battering ram that would come in to open the door; the other elements would finish the job. In theory, you could equip a single T cell with multiple chimeric antigen receptors and achieve even more precision. That’s something we would like to pursue.”
So, the Belgian researchers have a patent for two decades and, after it expires, more researchers could help to take the work further. Hmm …
Moving on, here’s a link to and a citation for the paper,
I have two bits about the Romans: the first is noted in the head for this posting and the second is about a chance to experience a Roman style classroom.
Empire of Letters
This January 8, 2019 news item on phys.org announces a book about how the technology of writing influenced how ancient Romans saw the world and provides a counterpoint to the notion that the ancient world (in Europe) was relentlessly oral in nature,
The Roman poet Lucretius’ epic work “De rerum natura,” or “On the Nature of Things,” is the oldest surviving scientific treatise written in Latin. Composed around 55 B.C.E., the text is a lengthy piece of contrarianism. Lucreutius was in the Epicurean school of philosophy: He wanted an account of the world rooted in earthly matter, rather than explanations based on the Gods and religion
Among other things, Lucretius believed in atomism, the idea that the world and cosmos consisted of minute pieces of matter, rather than four essential elements. To explain this point, Lucretius asked readers to think of bits of matter as being like letters of the alphabet. Indeed, both atoms and letters are called “elementa” in Latin—probably derived from the grouping of L,M, and N in the alphabet
To learn these elements of writing, students would copy out tables of letters and syllables, which Lucretius thought also served as a model for understanding the world, since matter and letters could be rearranged in parallel ways. For instance, Lucretius wrote, wood could be turned into fire by adding a little heat, while the word for wood, “lingum,” could be turned into the world for fire, “ignes,” by altering a few letters.
Students taking this analogy to heart would thus learn “the combinatory potential of nature and language,” says Stephanie Frampton, an associate professor of literature at MIT [Massachusetts Institute of Technology], in a new book on writing in the Roman world.
Moreover, Frampton emphasizes, the fact that students were learning all this specifically through writing exercises is a significant and underappreciated point in our understanding of ancient Rome: Writing, and the tools of writing, helped shape the Roman world.
“Everyone says the ancients are really into spoken and performed poetry, and don’t care about the written word,” Frampton says. “But look at Lucretius, who’s the first person writing a scientific text in Latin — the way that he explains his scientific insight is through this metaphor founded upon the written word.”
Frampton explores this and other connections between writing and Roman society in her new work, “Empire of Letters,” published last week by Oxford University Press [according to their webpage, the paper version will be published on February 4, 2019; the e-book is now available for purchase].
The book is a history of technology itself, as Frampton examines the particulars of Roman books — which often existed as scrolls back then — and their evolution over time. But a central focus of the work is how those technologies influenced how the Romans “thought about thought,” as she says.
Moreover, as Frampton notes, she is studying the history of Romans as “literate creatures,” which means studying the tools of writing used not just in completed works, but in education, too. The letter tables detailed by Lucretius are just one example of this. Romans also learned to read and write using wax tablets that they could wipe clean after exercises.
The need to wipe such tablets clean drove the Roman emphasis on learning the art of memory — including the “memory palace” method, which uses visualized locations for items to remember them, and which is still around today. For this reason Cicero, among other Roman writers, called memory and writing “most similar, though in a different medium.” As Frampton writes in the book, such tablets also produced “an intimate and complex relationship with memory” in the Roman world, and meant that “memory was a fundamental part of literary composition.”
Tablets also became a common Roman metaphor for how our brains work: They thought “the mind is like a wax tablet where you can write and erase and rewrite,” Frampton says. Understanding this kind of relationship between technology and the intellect, she thinks, helps us get that much closer to life as the Romans lived it
“I think it’s analagous to early computing,” Frampton says. “The way we talk about the mind now is that it’s a computer. … We think about the computer in the same way that [intellectuals] in Rome were thinking about writing on wax tablets.”
As Frampton discusses in the book, she believes the Romans did produce a number of physical innovations to the typical scroll-based back of the classic world, including changes in layout, format, coloring pigments, and possibly even book covers and the materials used as scroll handles, including ivory.
“The Romans were engineers, that’s [one thing] they were famous for,” Frampton says. “They are quite interesting and innovative in material culture.”
Looking beyond “Empire of Letters” itself, Frampton will co-teach an MIT undergraduate course in 2019, “Making Books,” that looks at the history of the book and gets students to use old technologies to produce books as they were once made. While that course has previously focused on printing-press technology, Frampton will help students go back even further in time, to the days of the scroll and codex, if they wish. All these reading devices, after all, were important innovations in their day.
“I’m working on old media,” Frampton says, “But those old media were once new.” [emphasis mine]
While the technologies Carolyn Marvin was writing about were not quite as old Frampton’s, she too noted the point about old and new technology in her 1990 book “When Old Technologies Were New” published by the Oxford University Press in 1990.
Getting back to Frampton, she has founded an organization known as the Materia Network, which is focused on (from @materianetwork’s Twitter description) “New Approaches to Material Text in the Roman World is a conference series and network for scholars of books and writing in Classical antiquity.”
You can find Materia here. They do have a Call for Proposals but I believe the deadline should read: December 20, 2018 (not 2019) since the conference will be held in April 2019).
I have a couple of final comments. (1) The grand daddy of oral and literate culture discussion is Walter J. Ong and I’m referring specifically to his 1982 book, Orality and Literacy. BTW, in addition to being a English Literature professor, the man was a Jesuit priest.
Reading Ancient Schoolroom
(2) The University of Reading (UK) has organized over the last few years, although they skipped in 2018, a series of events known as Reading Ancient Schoolroom (my August 9, 2018 posting features the ‘schoolroom’). The 2019 event is taking place January 23 – 25, 2019. You can find out more about the 2019 opportunity here. For anyone who can’t get to the UK easily, here’s a video of the Reading Ancient Schoolroom,
The Reading Ancient Schoolroom is a historically accurate reconstruction of an ancient schoolroom. It gives modern children an immersive experience of antiquity, acting the part of ancient children, wearing their clothes and using their writing equipment. It was developed by Eleanor Dickey at the University of Reading. Find out more at: www.readingancientschoolroom.com
The last time (June 18, 2018 post) I mentioned xenotransplantation (transplanting organs from one species into another species; see more here), it was in the context of an art/sci (or sciart) event coming to Vancouver (Canada).,
Patricia Piccinini’s Curious Imaginings Courtesy: Vancouver Biennale [downloaded from http://dailyhive.com/vancouver/vancouver-biennale-unsual-public-art-2018/]
The latest edition of the Vancouver Biennale was featured in a June 6, 2018 news item on the Daily Hive (Vancouver),
Melbourne artist Patricia Piccinini’s Curious Imaginings is expected to be one of the most talked about installations of the exhibit. Her style of “oddly captivating, somewhat grotesque, human-animal hybrid creature” is meant to be shocking and thought-provoking.
Piccinini’s interactive [emphasis mine] experience will “challenge us to explore the social impacts of emerging biotechnology and our ethical limits in an age where genetic engineering and digital technologies are already pushing the boundaries of humanity.”
Piccinini’s work will be displayed in the 105-year-old Patricia Hotel in Vancouver’s Strathcona neighbourhood. The 90-day ticketed exhibition [emphasis mine] is scheduled to open this September .
(The show opens on Sept. 14, 2018.)
At the time, I had yet to stumble across Ingfei Chen’s thoughtful dive into the topic in her May 9, 2018 article for Slate.com,
In the United States, the clock is ticking for more than 114,700 adults and children waiting for a donated kidney or other lifesaving organ, and each day, nearly 20 of them die. Researchers are devising a new way to grow human organs inside other animals, but the method raises potentially thorny ethical issues. Other conceivable futuristic techniques sound like dystopian science fiction. As we envision an era of regenerative medicine decades from now, how far is society willing to go to solve the organ shortage crisis?
I found myself pondering this question after a discussion about the promises of stem cell technologies veered from the intriguing into the bizarre. I was interviewing bioengineer Zev Gartner, co-director and research coordinator of the Center for Cellular Construction at the University of California, San Francisco, about so-called organoids, tiny clumps of organlike tissue that can self-assemble from human stem cells in a Petri dish. These tissue bits are lending new insights into how our organs form and diseases take root. Some researchers even hope they can nurture organoids into full-size human kidneys, pancreases, and other organs for transplantation.
Certain organoid experiments have recently set off alarm bells, but when I asked Gartner about it, his radar for moral concerns was focused elsewhere. For him, the “really, really thought-provoking” scenarios involve other emerging stem cell–based techniques for engineering replacement organs for people, he told me. “Like blastocyst complementation,” he said.
Never heard of it? Neither had I. Turns out it’s a powerful new genetic engineering trick that researchers hope to use for growing human organs inside pigs or sheep—organs that could be genetically personalized for transplant patients, in theory avoiding immune-system rejection problems. The science still has many years to go, but if it pans out, it could be one solution to the organ shortage crisis. However, the prospect of creating hybrid animals with human parts and killing them to harvest organs has already raised a slew of ethical questions. In 2015, the National Institutes of Health placed a moratorium on federal funding of this nascent research area while it evaluated and discussed the issues.
As Gartner sees it, the debate over blastocyst complementation research—work that he finds promising—is just one of many conversations that society needs to have about the ethical and social costs and benefits of future technologies for making lifesaving transplant organs. “There’s all these weird ways that we could go about doing this,” he said, with a spectrum of imaginable approaches that includes organoids, interspecies organ farming, and building organs from scratch using 3D bioprinters. But even if it turns out we can produce human organs in these novel ways, the bigger issue, in each technological instance, may be whether we should.
Gartner crystallized things with a downright creepy example: “We know that the best bioreactor for tissues and organs for humans are human beings,” he said. Hypothetically, “the best way to get you a new heart would be to clone you, grow up a copy of yourself, and take the heart out.” [emphasis mine] Scientists could probably produce a cloned person with the technologies we already have, if money and ethics were of no concern. “But we don’t want to go there, right?” he added in the next breath. “The ethics involved in doing it are not compatible with who we want to be as a society.”
This sounds like Gartner may have been reading some science fiction, specifically, Lois McMaster Bujold and her Barrayar series where she often explored the ethics and possibilities of bioengineering. At this point, some of her work seems eerily prescient.
As for Chen’s article, I strongly encourage you to read it in its entirety if you have the time.
Medicine, healing, and big money
At about the same time, there was a May 31, 2018 news item on phys.org offering a perspective from some of the leaders in the science and the business (Note: Links have been removed),
Over the past few years, researchers led by George Church have made important strides toward engineering the genomes of pigs to make their cells compatible with the human body. So many think that it’s possible that, with the help of CRISPR technology, a healthy heart for a patient in desperate need might one day come from a pig.
“It’s relatively feasible to change one gene in a pig, but to change many dozens—which is quite clear is the minimum here—benefits from CRISPR,” an acronym for clustered regularly interspaced short palindromic repeats, said Church, the Robert Winthrop Professor of Genetics at Harvard Medical School (HMS) and a core faculty member of Harvard’s Wyss Institute for Biologically Inspired Engineering. Xenotransplantation is “one of few” big challenges (along with gene drives and de-extinction, he said) “that really requires the ‘oomph’ of CRISPR.”
To facilitate the development of safe and effective cells, tissues, and organs for future medical transplantation into human patients, Harvard’s Office of Technology Development has granted a technology license to the Cambridge biotech startup eGenesis.
Co-founded by Church and former HMS doctoral student Luhan Yang in 2015, eGenesis announced last year that it had raised $38 million to advance its research and development work. At least eight former members of the Church lab—interns, doctoral students, postdocs, and visiting researchers—have continued their scientific careers as employees there.
“The Church Lab is well known for its relentless pursuit of scientific achievements so ambitious they seem improbable—and, indeed, [for] its track record of success,” said Isaac Kohlberg, Harvard’s chief technology development officer and senior associate provost. “George deserves recognition too for his ability to inspire passion and cultivate a strong entrepreneurial drive among his talented research team.”
The license from Harvard OTD covers a powerful set of genome-engineering technologies developed at HMS and the Wyss Institute, including access to foundational intellectual property relating to the Church Lab’s 2012 breakthrough use of CRISPR, led by Yang and Prashant Mali, to edit the genome of human cells. Subsequent innovations that enabled efficient and accurate editing of numerous genes simultaneously are also included. The license is exclusive to eGenesis but limited to the field of xenotransplantation.
The prospect of using living, nonhuman organs, and concerns over the infectiousness of pathogens either present in the tissues or possibly formed in combination with human genetic material, have prompted the Food and Drug Administration to issue detailed guidance on xenotransplantation research and development since the mid-1990s. In pigs, a primary concern has been that porcine endogenous retroviruses (PERVs), strands of potentially pathogenic DNA in the animals’ genomes, might infect human patients and eventually cause disease. [emphases mine]
That’s where the Church lab’s CRISPR expertise has enabled significant advances. In 2015, the lab published important results in the journal Science, successfully demonstrating the use of genome engineering to eliminate all 62 PERVs in porcine cells. Science later called it “the most widespread CRISPR editing feat to date.”
In 2017, with collaborators at Harvard, other universities, and eGenesis, Church and Yang went further. Publishing again in Science, they first confirmed earlier researchers’ fears: Porcine cells can, in fact, transmit PERVs into human cells, and those human cells can pass them on to other, unexposed human cells. (It is still unknown under what circumstances those PERVs might cause disease.) In the same paper, they corrected the problem, announcing the embryogenesis and birth of 37 PERV-free pigs. [Note: My July 17, 2018 post features research which suggests CRISPR-Cas9 gene editing may cause greater genetic damage than had been thought.]
“Taken together, those innovations were stunning,” said Vivian Berlin, director of business development in OTD, who manages the commercialization strategy for much of Harvard’s intellectual property in the life sciences. “That was the foundation they needed, to convince both the scientific community and the investment community that xenotransplantation might become a reality.”
“After hundreds of tests, this was a critical milestone for eGenesis — and the entire field — and represented a key step toward safe organ transplantation from pigs,” said Julie Sunderland, interim CEO of eGenesis. “Building on this study, we hope to continue to advance the science and potential of making xenotransplantation a safe and routine medical procedure.”
Genetic engineering may undercut human diseases, but also could help restore extinct species, researcher says. [Shades of the Jurassic Park movies!]
It’s not, however, the end of the story: An immunological challenge remains, which eGenesis will need to address. The potential for a patient’s body to outright reject transplanted tissue has stymied many previous attempts at xenotransplantation. Church said numerous genetic changes must be achieved to make porcine organs fully compatible with human patients. Among these are edits to several immune functions, coagulation functions, complements, and sugars, as well as the PERVs.
“Trying the straight transplant failed almost immediately, within hours, because there’s a huge mismatch in the carbohydrates on the surface of the cells, in particular alpha-1-3-galactose, and so that was a showstopper,” Church explained. “When you delete that gene, which you can do with conventional methods, you still get pretty fast rejection, because there are a lot of other aspects that are incompatible. You have to take care of each of them, and not all of them are just about removing things — some of them you have to humanize. There’s a great deal of subtlety involved so that you get normal pig embryogenesis but not rejection.
“Putting it all together into one package is challenging,” he concluded.
In short, it’s the next big challenge for CRISPR.
Not unexpectedly, there is no mention of the CRISPR patent fight between Harvard/MIT’s (Massachusetts Institute of Technology) Broad Institute and the University of California at Berkeley (UC Berkeley). My March 15, 2017 posting featured an outcome where the Broad Institute won the first round of the fight. As I recall, it was a decision based on the principles associated with King Solomon, i.e., the US Patent Office, divided the baby and UCBerkeley got the less important part of the baby. As you might expect the decision has been appealed. In an April 30, 2018 piece, Scientific American reprinted an article about the latest round in the fight written by Sharon Begley for STAT (Note: Links have been removed),
All You Need to Know for Round 2 of the CRISPR Patent Fight
It’s baaaaack, that reputation-shredding, stock-moving fight to the death over key CRISPR patents. On Monday morning in Washington, D.C., the U.S. Court of Appeals for the Federal Circuit will hear oral arguments in University of California v. Broad Institute. Questions?
How did we get here? The patent office ruled in February 2017 that the Broad’s 2014 CRISPR patent on using CRISPR-Cas9 to edit genomes, based on discoveries by Feng Zhang, did not “interfere” with a patent application by UC based on the work of UC Berkeley’s Jennifer Doudna. In plain English, that meant the Broad’s patent, on using CRISPR-Cas9 to edit genomes in eukaryotic cells (all animals and plants, but not bacteria), was different from UC’s, which described Doudna’s experiments using CRISPR-Cas9 to edit DNA in a test tube—and it was therefore valid. The Patent Trial and Appeal Board concluded that when Zhang got CRISPR-Cas9 to work in human and mouse cells in 2012, it was not an obvious extension of Doudna’s earlier research, and that he had no “reasonable expectation of success.” UC appealed, and here we are.
For anyone who may not realize what the stakes are for these institutions, Linda Williams in a March 16, 1999 article for the LA Times had this to say about universities, patents, and money,
The University of Florida made about $2 million last year in royalties on a patent for Gatorade Thirst Quencher, a sports drink that generates some $500 million to $600 million a year in revenue for Quaker Oats Co.
The payments place the university among the top five in the nation in income from patent royalties.
Oh, but if some people on the Gainesville, Fla., campus could just turn back the clock. “If we had done Gatorade right, we would be getting $5 or $6 million (a year),” laments Donald Price, director of the university’s office of corporate programs. “It is a classic example of how not to handle a patent idea,” he added.
Gatorade was developed in 1965 when many universities were ill equipped to judge the commercial potential of ideas emerging from their research labs. Officials blew the university’s chance to control the Gatorade royalties when they declined to develop a professor’s idea.
The Gatorade story does not stop there and, even though it’s almost 20 years old, this article stands the test of time. I strongly encourage you to read it if the business end of patents and academia interest you or if you would like to develop more insight into the Broad Institute/UC Berkeley situation.
Getting back to the science, there is that pesky matter of diseases crossing over from one species to another. While, Harvard and eGenesis claim a victory in this area, it seems more work needs to be done.
A shortage of organs for transplantation — including kidneys and hearts — means that many patients die while still on waiting lists. So, research at the University of Alabama at Birmingham and other sites has turned to pig organs as an alternative. [emphasis mine]
Using gene-editing, researchers have modified such organs to prevent rejection, and research with primates shows the modified pig organs are well-tolerated.
An added step is needed to ensure the safety of these inter-species transplants — sensitive, quantitative assays for viruses and other infectious microorganisms in donor pigs that potentially could gain access to humans during transplantation.
The U.S. Food and Drug Administration requires such testing, prior to implantation, of tissues used for xenotransplantation from animals to humans. It is possible — though very unlikely — that an infectious agent in transplanted tissues could become an emerging infectious disease in humans.
In a paper published in Xenotransplantation, Mark Prichard, Ph.D., and colleagues at UAB have described the development and testing of 30 quantitative assays for pig infectious agents. These assays had sensitivities similar to clinical lab assays for viral loads in human patients. After validation, the UAB team also used the assays on nine sows and 22 piglets delivered from the sows through caesarian section.
“Going forward, ensuring the safety of these organs is of paramount importance,” Prichard said. “The use of highly sensitive techniques to detect potential pathogens will help to minimize adverse events in xenotransplantation.”
“The assays hold promise as part of the screening program to identify suitable donor animals, validate and release transplantable organs for research purposes, and monitor transplant recipients,” said Prichard, a professor in the UAB Department of Pediatrics and director of the Department of Pediatrics Molecular Diagnostics Laboratory.
The UAB researchers developed quantitative polymerase chain reaction, or qPCR, assays for 28 viruses sometimes found in pigs and two groups of mycoplasmas. They established reproducibility, sensitivity, specificity and lower limit of detection for each assay. All but three showed features of good quantitative assays, and the lower limit of detection values ranged between one and 16 copies of the viral or bacterial genetic material.
Also, the pig virus assays did not give false positives for some closely related human viruses.
As a start to understanding the infectious disease load in normal healthy animals and ensuring the safety of pig tissues used in xenotransplantation research, the researchers then screened blood, nasal swab and stool specimens from nine adult sows and 22 of their piglets delivered by caesarian section.
Mycoplasma species and two distinct herpesviruses were the most commonly detected microorganisms. Yet 14 piglets that were delivered from three sows infected with either or both herpesviruses were not infected with the herpesviruses, showing that transmission of these viruses from sow to the caesarian-delivery piglet was inefficient.
Prichard says the assays promise to enhance the safety of pig tissues for xenotransplantation, and they will also aid evaluation of human specimens after xenotransplantation.
The UAB researchers say they subsequently have evaluated more than 300 additional specimens, and that resulted in the detection of most of the targets. “The detection of these targets in pig specimens provides reassurance that the analytical methods are functioning as designed,” said Prichard, “and there is no a priori reason some targets might be more difficult to detect than others with the methods described here.”
As is my custom, here’s a link to and a citation for the paper,
All this leads to questions about chimeras. If a pig is incubating organs with human cells it’s a chimera but then means the human receiving the organ becomes a chimera too. (For an example, see my Dec. 22, 2013 posting where there’s mention of a woman who received a trachea from a pig. Scroll down about 30% of the way.)
What is it to be human?
A question much beloved of philosophers and others, the question seems particularly timely with xenotransplantion and other developments such neuroprosthetics (cyborgs) and neuromorphic computing (brainlike computing).
As I’ve noted before, although not recently, popular culture offers a discourse on these issues. Take a look at the superhero movies and the way in which enhanced humans and aliens are presented. For example, X-Men comics and movies present mutants (humans with enhanced abilities) as despised and rejected. Video games (not really my thing but there is the Deus Ex series which has as its hero, a cyborg also offer insight into these issues.
Other than popular culture and in the ‘bleeding edge’ arts community, I can’t recall any public discussion on these matters arising from the extraordinary set of technologies which are being deployed or prepared for deployment in the foreseeable future.
(If you’re in Vancouver (Canada) from September 14 – December 15, 2018, you may want to check out Piccinini’s work. Also, there’s ” NCSU [North Carolina State University] Libraries, NC State’s Genetic Engineering and Society (GES) Center, and the Gregg Museum of Art & Design have issued a public call for art for the upcoming exhibition Art’s Work in the Age of Biotechnology: Shaping our Genetic Futures.” from my Sept. 6, 2018 posting. Deadline: Oct. 1, 2018.)
At a guess, there will be pushback from people who have no interest in debating what it is to be human as they already know, and will find these developments, when they learn about them, to be horrifying and unnatural.