Tag Archives: Harvard University

Need to improve oversight on chimeric human-animal research

It seems chimeras are of more interest these days. In all likelihood that has something to do with the fellow who received a transplant of a pig’s heart in January 2022 (he died in March 2022).

For those who aren’t familiar with the term, a chimera is an entity with two different DNA (deoxyribonucleic acid) identities. In short, if you get a DNA sample from the heart, it’s different from a DNA sample obtained from a cheek swab. This contrasts with a hybrid such as a mule (donkey/horse) whose DNA samples show a consisted identity throughout its body.

A December 12, 2022 The Hastings Center news release (also on EurekAlert) announces a special report,

A new report on the ethics of crossing species boundaries by inserting human cells into nonhuman animals – research surrounded by debate – makes recommendations clarifying the ethical issues and calling for improved oversight of this work.

The report, “Creating Chimeric Animals — Seeking Clarity On Ethics and Oversight,” was developed by an interdisciplinary team, with funding from the National Institutes of Health. Principal investigators are Josephine Johnston and Karen Maschke, research scholars at The Hastings Center, and Insoo Hyun, director of the Center for Life Sciences and Public Learning at the Museum of Life Sciences in Boston, formerly of Case Western Reserve University.

Advances in human stem cell science and gene editing enable scientists to insert human cells more extensively and precisely into nonhuman animals, creating “chimeric” animals, embryos, and other organisms that contain a mix of human and nonhuman cells.

Many people hope that this research will yield enormous benefits, including better models of human disease, inexpensive sources of human eggs and embryos for research, and sources of tissues and organs suitable for transplantation into humans. 

But there are ethical concerns about this type of research, which raise questions such as whether the moral status of nonhuman animals is altered by the insertion of human stem cells, whether these studies should be subject to additional prohibitions or oversight, and whether this kind of research should be done at all.

The report found that:

Animal welfare is a primary ethical issue and should be a focus of ethical and policy analysis as well as the governance and oversight of chimeric research.

Chimeric studies raise the possibility of unique or novel harms resulting from the insertion and development of human stem cells in nonhuman animals, particularly when those cells develop in the brain or central nervous system.

Oversight and governance of chimeric research are siloed, and public communication is minimal. Public communication should be improved, communication between the different committees involved in oversight at each institution should be enhanced, and a national mechanism created for those involved in oversight of these studies. 

Scientists, journalists, bioethicists, and others writing about chimeric research should use precise and accessible language that clarifies rather than obscures the ethical issues at stake. The terms “chimera,” which in Greek mythology refers to a fire-breathing monster, and “humanization” are examples of ethically laden, or overly broad language to be avoided.

The Research Team

The Hastings Center

• Josephine Johnston
• Karen J. Maschke
• Carolyn P. Neuhaus
• Margaret M. Matthews
• Isabel Bolo

Case Western Reserve University
• Insoo Hyun (now at Museum of Science, Boston)
• Patricia Marshall
• Kaitlynn P. Craig

The Work Group

• Kara Drolet, Oregon Health & Science University
• Henry T. Greely, Stanford University
• Lori R. Hill, MD Anderson Cancer Center
• Amy Hinterberger, King’s College London
• Elisa A. Hurley, Public Responsibility in Medicine and Research
• Robert Kesterson, University of Alabama at Birmingham
• Jonathan Kimmelman, McGill University
• Nancy M. P. King, Wake Forest University School of Medicine
• Geoffrey Lomax, California Institute for Regenerative Medicine
• Melissa J. Lopes, Harvard University Embryonic Stem Cell Research Oversight Committee
• P. Pearl O’Rourke, Harvard Medical School
• Brendan Parent, NYU Grossman School of Medicine
• Steven Peckman, University of California, Los Angeles
• Monika Piotrowska, State University of New York at Albany
• May Schwarz, The Salk Institute for Biological Studies
• Jeff Sebo, New York University
• Chris Stodgell, University of Rochester
• Robert Streiffer, University of Wisconsin-Madison
• Lorenz Studer, Memorial Sloan Kettering Cancer Center
• Amy Wilkerson, The Rockefeller University

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

Creating Chimeric Animals: Seeking Clarity on Ethics and Oversight edited by Karen J. Maschke, Margaret M. Matthews, Kaitlynn P. Craig, Carolyn P. Neuhaus, Insoo Hyun, Josephine Johnston, The Hastings Center Report Volume 52, Issue S2 (Special Report), November‐December 2022 First Published: 09 December 2022

This report is open access.

Water-based ionic computing (neural computing networks)

An ionic circuit comprising hundreds of ionic transistors
Caption: An ionic circuit comprising hundreds of ionic transistors. Credit: Woo-Bin Jung/Harvard SEAS

I love that image and it pertains to this September 29, 2022 news item on ScienceDaily,

Microprocessors in smartphones, computers, and data centers process information by manipulating electrons through solid semiconductors but our brains have a different system. They rely on the manipulation of ions in liquid to process information.

Inspired by the brain, researchers have long been seeking to develop ‘ionics’ in an aqueous solution. While ions in water move slower than electrons in semiconductors, scientists think the diversity of ionic species with different physical and chemical properties could be harnessed for richer and more diverse information processing.

Ionic computing, however, is still in its early days. To date, labs have only developed individual ionic devices such as ionic diodes and transistors, but no one has put many such devices together into a more complex circuit for computing — until now.

A team of researchers at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), in collaboration with DNA Script, a biotech startup, have developed an ionic circuit comprising hundreds of ionic transistors and performed a core process of neural net computing.

A September 28, 2022 Harvard John A. Paulson School of Engineering and Applied Sciences news release (also on EurekAlert but published on Sept. 29, 2022), which originated the news item, provides details (Note: A link has been removed),

The researchers began by building a new type of ionic transistor from a  technique they recently pioneered. The transistor consists of an aqueous solution of quinone molecules, interfaced with two concentric ring electrodes with a center disk electrode, like a bullseye. The two ring electrodes electrochemically lower and tune the local pH around the center disk by producing and trapping hydrogen ions. A voltage applied to the center disk causes an electrochemical reaction to generate an ionic current from the disk into the water. The reaction rate can be sped up or down –– increasing or decreasing the ionic current — by tuning the local pH.  In other words, the pH controls, or gates, the disk’s ionic current in the aqueous solution, creating an ionic counterpart of the electronic transistor.

They then engineered the pH-gated ionic transistor in such a way that the disk current is an arithmetic multiplication of the disk voltage and a “weight” parameter representing the local pH gating the transistor. They organized these transistors into a 16 × 16 array to expand the analog arithmetic multiplication of individual transistors into an analog matrix multiplication, with the array of local pH values serving as a weight matrix encountered in neural networks.

“Matrix multiplication is the most prevalent calculation in neural networks for artificial intelligence,” said Woo-Bin Jung, a postdoctoral fellow at SEAS and the first author of the paper. “Our ionic circuit performs the matrix multiplication in water in an analog manner that is based fully on electrochemical machinery.”

“Microprocessors manipulate electrons in a digital fashion to perform matrix multiplication,” said Donhee Ham, the Gordon McKay Professor of Electrical Engineering and Applied Physics at SEAS and the senior author of the paper. “While our ionic circuit cannot be as fast or accurate as the digital microprocessors, the electrochemical matrix multiplication in water is charming in its own right, and has a potential to be energy efficient.”

Now, the team looks to enrich the chemical complexity of the system.

“So far, we have used only 3 to 4 ionic species, such as hydrogen and quinone ions, to enable the gating and ionic transport in the aqueous ionic transistor,” said Jung. “It will be very interesting to employ more diverse ionic species and to see how we can exploit them to make rich the contents of information to be processed.”

The research was co-authored by Han Sae Jung, Jun Wang, Henry Hinton, Maxime Fournier, Adrian Horgan, Xavier Godron, and Robert Nicol. It was supported in part by the Office of the Director of National Intelligence (ODNI), Intelligence Advanced Research Projects Activity (IARPA), under grant 2019-19081900002.

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

An Aqueous Analog MAC Machine by Woo-Bin Jung, Han Sae Jung, Jun Wang, Henry Hinton, Maxime Fournier, Adrian Horgan, Xavier Godron, Robert Nicol, Donhee Ham. Advanced Materials DOI: https://doi.org/10.1002/adma.202205096 First published online: 23 August 2022

This paper is behind a paywall.

As for the biotech startup mentioned as a collaborative partner in the research, DNA Script can be found here.

A CRISPR (clustered regularly interspaced short palindromic repeats) anniversary

June 2022 was the 10th anniversary of the publication of a study the paved the way for CRISPR-Cas9 gene editing and Sophie Fessl’s June 28, 2022 article for The Scientist offers a brief history (Note: Links have been removed),

Ten years ago, Emmanuelle Charpentier and Jennifer Doudna published the study that paved the way for a new kind of genome editing: the suite of technologies now known as CRISPR. Writing in [the journal] Science, they adapted an RNA-mediated bacterial immune defense into a targeted DNA-altering system. “Our study . . . highlights the potential to exploit the system for RNA-programmable genome editing,” they conclude in the abstract of their paper—a potential that, in the intervening years, transformed the life sciences. 

From gene drives to screens, and diagnostics to therapeutics, CRISPR nucleic acids and the Cas enzymes with which they’re frequently paired have revolutionized how scientists tinker with DNA and RNA. … altering the code of life with CRISPR has been marred by ethical concerns. Perhaps the most prominent example was when Chinese scientist He Jiankui created the first gene edited babies using CRISPR/Cas9 genome editing. Doudna condemned Jiankui’s work, for which he was jailed, as “risky and medically unnecessary” and a “shocking reminder of the scientific and ethical challenges raised by this powerful technology.” 

There’s also the fact that legal battles over who gets to claim ownership of the system’s many applications have persisted almost as long as the technology has been around. Both Doudna and Charpentier’s teams from the University of California, Berkeley, and the University of Vienna and a team led by the Broad Institute’s Feng Zhang claim to be the first to have adapted CRISPR-Cas9 for gene editing in complex cells (eukaryotes). Patent offices in different countries have reached varying decisions, but in the US, the latest rulings say that the Broad Institute of MIT [Massachusetts Institute of Technology] and Harvard retains intellectual property of using CRISPR-Cas9 in eukaryotes, while Emmanuelle Charpentier, the University of California, and the University of Vienna maintain their original patent over using CRISPR-Cas9 for editing in vitro and in prokaryotes. 

Still, despite the controversies, the technique continues to be explored academically and commercially for everything from gene therapy to crop improvement. Here’s a look at seven different ways scientists have utilized CRISPR.

Fessl goes on to give a brief overview of CRISPR and gene drives, genetic screens, diagnostics, including COVID-19 tests, gene therapy, therapeutics, crop and livestock improvement, and basic research.

For anyone interested in the ethical issues (with an in depth look at the Dr. He Jiankui story), I suggest reading either or both Eben Kirksey’s 2020 book, “The Mutant Project; Inside the Global Race to Genetically Modify Humans,”

An anthropologist visits the frontiers of genetics, medicine, and technology to ask: Whose values are guiding gene editing experiments? And what does this new era of scientific inquiry mean for the future of the human species?

“That rare kind of scholarship that is also a page-turner.”
—Britt Wray, author of Rise of the Necrofauna

At a conference in Hong Kong in November 2018, Dr. He Jiankui announced that he had created the first genetically modified babies—twin girls named Lulu and Nana—sending shockwaves around the world. A year later, a Chinese court sentenced Dr. He to three years in prison for “illegal medical practice.”

As scientists elsewhere start to catch up with China’s vast genetic research program, gene editing is fueling an innovation economy that threatens to widen racial and economic inequality. Fundamental questions about science, health, and social justice are at stake: Who gets access to gene editing technologies? As countries loosen regulations around the globe, from the U.S. to Indonesia, can we shape research agendas to promote an ethical and fair society?

Eben Kirksey takes us on a groundbreaking journey to meet the key scientists, lobbyists, and entrepreneurs who are bringing cutting-edge genetic engineering tools like CRISPR—created by Nobel Prize-winning biochemists Jennifer Doudna and Emmanuelle Charpentier—to your local clinic. He also ventures beyond the scientific echo chamber, talking to disabled scholars, doctors, hackers, chronically-ill patients, and activists who have alternative visions of a genetically modified future for humanity.

and/or Kevin Davies’s 2020 book, “Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing,”

One of the world’s leading experts on genetics unravels one of the most important breakthroughs in modern science and medicine. 

If our genes are, to a great extent, our destiny, then what would happen if mankind could engineer and alter the very essence of our DNA coding? Millions might be spared the devastating effects of hereditary disease or the challenges of disability, whether it was the pain of sickle-cell anemia to the ravages of Huntington’s disease.

But this power to “play God” also raises major ethical questions and poses threats for potential misuse. For decades, these questions have lived exclusively in the realm of science fiction, but as Kevin Davies powerfully reveals in his new book, this is all about to change.

Engrossing and page-turning, Editing Humanity takes readers inside the fascinating world of a new gene editing technology called CRISPR, a high-powered genetic toolkit that enables scientists to not only engineer but to edit the DNA of any organism down to the individual building blocks of the genetic code.

Davies introduces readers to arguably the most profound scientific breakthrough of our time. He tracks the scientists on the front lines of its research to the patients whose powerful stories bring the narrative movingly to human scale.

Though the birth of the “CRISPR babies” in China made international news, there is much more to the story of CRISPR than headlines seemingly ripped from science fiction. In Editing Humanity, Davies sheds light on the implications that this new technology can have on our everyday lives and in the lives of generations to come.

Kevin Davies is the executive editor of The CRISPR Journal and the founding editor of Nature Genetics. He holds an MA in biochemistry from the University of Oxford and a PhD in molecular genetics from the University of London. He is the author of Cracking the Genome, The $1,000 Genome, and co-authored a new edition of DNA: The Story of the Genetic Revolution with Nobel Laureate James D. Watson and Andrew Berry. In 2017, Kevin was selected for a Guggenheim Fellowship in science writing.

I’ve read both books and while some of the same ground is covered, the perspectives diverge somewhat. Both authors offer a more nuanced discussion of the issues than was the case in the original reporting about Dr. He’s work.

Reconfiguring a LEGO-like AI chip with light

MIT engineers have created a reconfigurable AI chip that comprises alternating layers of sensing and processing elements that can communicate with each other. Credit: Figure courtesy of the researchers and edited by MIT News

This image certainly challenges any ideas I have about what Lego looks like. It seems they see things differently at the Massachusetts Institute of Technology (MIT). From a June 13, 2022 MIT news release (also on EurekAlert),

Imagine a more sustainable future, where cellphones, smartwatches, and other wearable devices don’t have to be shelved or discarded for a newer model. Instead, they could be upgraded with the latest sensors and processors that would snap onto a device’s internal chip — like LEGO bricks incorporated into an existing build. Such reconfigurable chipware could keep devices up to date while reducing our electronic waste. 

Now MIT engineers have taken a step toward that modular vision with a LEGO-like design for a stackable, reconfigurable artificial intelligence chip.

The design comprises alternating layers of sensing and processing elements, along with light-emitting diodes (LED) that allow for the chip’s layers to communicate optically. Other modular chip designs employ conventional wiring to relay signals between layers. Such intricate connections are difficult if not impossible to sever and rewire, making such stackable designs not reconfigurable.

The MIT design uses light, rather than physical wires, to transmit information through the chip. The chip can therefore be reconfigured, with layers that can be swapped out or stacked on, for instance to add new sensors or updated processors.

“You can add as many computing layers and sensors as you want, such as for light, pressure, and even smell,” says MIT postdoc Jihoon Kang. “We call this a LEGO-like reconfigurable AI chip because it has unlimited expandability depending on the combination of layers.”

The researchers are eager to apply the design to edge computing devices — self-sufficient sensors and other electronics that work independently from any central or distributed resources such as supercomputers or cloud-based computing.

“As we enter the era of the internet of things based on sensor networks, demand for multifunctioning edge-computing devices will expand dramatically,” says Jeehwan Kim, associate professor of mechanical engineering at MIT. “Our proposed hardware architecture will provide high versatility of edge computing in the future.”

The team’s results are published today in Nature Electronics. In addition to Kim and Kang, MIT authors include co-first authors Chanyeol Choi, Hyunseok Kim, and Min-Kyu Song, and contributing authors Hanwool Yeon, Celesta Chang, Jun Min Suh, Jiho Shin, Kuangye Lu, Bo-In Park, Yeongin Kim, Han Eol Lee, Doyoon Lee, Subeen Pang, Sang-Hoon Bae, Hun S. Kum, and Peng Lin, along with collaborators from Harvard University, Tsinghua University, Zhejiang University, and elsewhere.

Lighting the way

The team’s design is currently configured to carry out basic image-recognition tasks. It does so via a layering of image sensors, LEDs, and processors made from artificial synapses — arrays of memory resistors, or “memristors,” that the team previously developed, which together function as a physical neural network, or “brain-on-a-chip.” Each array can be trained to process and classify signals directly on a chip, without the need for external software or an Internet connection.

In their new chip design, the researchers paired image sensors with artificial synapse arrays, each of which they trained to recognize certain letters — in this case, M, I, and T. While a conventional approach would be to relay a sensor’s signals to a processor via physical wires, the team instead fabricated an optical system between each sensor and artificial synapse array to enable communication between the layers, without requiring a physical connection. 

“Other chips are physically wired through metal, which makes them hard to rewire and redesign, so you’d need to make a new chip if you wanted to add any new function,” says MIT postdoc Hyunseok Kim. “We replaced that physical wire connection with an optical communication system, which gives us the freedom to stack and add chips the way we want.”

The team’s optical communication system consists of paired photodetectors and LEDs, each patterned with tiny pixels. Photodetectors constitute an image sensor for receiving data, and LEDs to transmit data to the next layer. As a signal (for instance an image of a letter) reaches the image sensor, the image’s light pattern encodes a certain configuration of LED pixels, which in turn stimulates another layer of photodetectors, along with an artificial synapse array, which classifies the signal based on the pattern and strength of the incoming LED light.

Stacking up

The team fabricated a single chip, with a computing core measuring about 4 square millimeters, or about the size of a piece of confetti. The chip is stacked with three image recognition “blocks,” each comprising an image sensor, optical communication layer, and artificial synapse array for classifying one of three letters, M, I, or T. They then shone a pixellated image of random letters onto the chip and measured the electrical current that each neural network array produced in response. (The larger the current, the larger the chance that the image is indeed the letter that the particular array is trained to recognize.)

The team found that the chip correctly classified clear images of each letter, but it was less able to distinguish between blurry images, for instance between I and T. However, the researchers were able to quickly swap out the chip’s processing layer for a better “denoising” processor, and found the chip then accurately identified the images.

“We showed stackability, replaceability, and the ability to insert a new function into the chip,” notes MIT postdoc Min-Kyu Song.

The researchers plan to add more sensing and processing capabilities to the chip, and they envision the applications to be boundless.

“We can add layers to a cellphone’s camera so it could recognize more complex images, or makes these into healthcare monitors that can be embedded in wearable electronic skin,” offers Choi, who along with Kim previously developed a “smart” skin for monitoring vital signs.

Another idea, he adds, is for modular chips, built into electronics, that consumers can choose to build up with the latest sensor and processor “bricks.”

“We can make a general chip platform, and each layer could be sold separately like a video game,” Jeehwan Kim says. “We could make different types of neural networks, like for image or voice recognition, and let the customer choose what they want, and add to an existing chip like a LEGO.”

This research was supported, in part, by the Ministry of Trade, Industry, and Energy (MOTIE) from South Korea; the Korea Institute of Science and Technology (KIST); and the Samsung Global Research Outreach Program.

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

Reconfigurable heterogeneous integration using stackable chips with embedded artificial intelligence by Chanyeol Choi, Hyunseok Kim, Ji-Hoon Kang, Min-Kyu Song, Hanwool Yeon, Celesta S. Chang, Jun Min Suh, Jiho Shin, Kuangye Lu, Bo-In Park, Yeongin Kim, Han Eol Lee, Doyoon Lee, Jaeyong Lee, Ikbeom Jang, Subeen Pang, Kanghyun Ryu, Sang-Hoon Bae, Yifan Nie, Hyun S. Kum, Min-Chul Park, Suyoun Lee, Hyung-Jun Kim, Huaqiang Wu, Peng Lin & Jeehwan Kim. Nature Electronics volume 5, pages 386–393 (2022) 05 May 2022 Issue Date: June 2022 Published: 13 June 2022 DOI: https://doi.org/10.1038/s41928-022-00778-y

This paper is behind a paywall.

Kempner Institute for the Study of Natural and Artificial Intelligence launched at Harvard University and University of Manchester pushes the boundaries of smart robotics and AI

Before getting to the two news items, it might be a good idea to note that ‘artificial intelligence (AI)’ and ‘robot’ are not synonyms although they are often used that way, even by people who should know better. (sigh … I do it too)

A robot may or may not be animated with artificial intelligence while artificial intelligence algorithms may be installed on a variety of devices such as a phone or a computer or a thermostat or a … .

It’s something to bear in mind when reading about the two new institutions being launched. Now, on to Harvard University.

Kempner Institute for the Study of Natural and Artificial Intelligence

A September 23, 2022 Chan Zuckerberg Initiative (CZI) news release (also on EurekAlert) announces a symposium to launch a new institute close to Mark Zuckerberg’s heart,

On Thursday [September 22, 2022], leadership from the Chan Zuckerberg Initiative (CZI) and Harvard University celebrated the launch of the Kempner Institute for the Study of Natural and Artificial Intelligence at Harvard University with a symposium on Harvard’s campus. Speakers included CZI Head of Science Stephen Quake, President of Harvard University Lawrence Bacow, Provost of Harvard University Alan Garber, and Kempner Institute co-directors Bernardo Sabatini and Sham Kakade. The event also included remarks and panels from industry leaders in science, technology, and artificial intelligence, including Bill Gates, Eric Schmidt, Andy Jassy, Daniel Huttenlocher, Sam Altman, Joelle Pineau, Sangeeta Bhatia, and Yann LeCun, among many others.

The Kempner Institute will seek to better understand the basis of intelligence in natural and artificial systems. Its bold premise is that the two fields are intimately interconnected; the next generation of AI will require the same principles that our brains use for fast, flexible natural reasoning, and understanding how our brains compute and reason requires theories developed for AI. The Kempner Institute will study AI systems, including artificial neural networks, to develop both principled theories [emphasis mine] and a practical understanding of how these systems operate and learn. It will also focus on research topics such as learning and memory, perception and sensation, brain function, and metaplasticity. The Institute will recruit and train future generations of researchers from undergraduates and graduate students to post-docs and faculty — actively recruiting from underrepresented groups at every stage of the pipeline — to study intelligence from biological, cognitive, engineering, and computational perspectives.

CZI Co-Founder and Co-CEO Mark Zuckerberg [chairman and chief executive officer of Meta/Facebook] said: “The Kempner Institute will be a one-of-a-kind institute for studying intelligence and hopefully one that helps us discover what intelligent systems really are, how they work, how they break and how to repair them. There’s a lot of exciting implications because once you understand how something is supposed to work and how to repair it once it breaks, you can apply that to the broader mission the Chan Zuckerberg Initiative has to empower scientists to help cure, prevent or manage all diseases.”

CZI Co-Founder and Co-CEO Priscilla Chan said: “Just attending this school meant the world to me. But to stand on this stage and to be able to give something back is truly a dream come true … All of this progress starts with building one fundamental thing: a Kempner community that’s diverse, multi-disciplinary and multi-generational, because incredible ideas can come from anyone. If you bring together people from all different disciplines to look at a problem and give them permission to articulate their perspective, you might start seeing insights or solutions in a whole different light. And those new perspectives lead to new insights and discoveries and generate new questions that can lead an entire field to blossom. So often, that momentum is what breaks the dam and tears down old orthodoxies, unleashing new floods of new ideas that allow us to progress together as a society.”

CZI Head of Science Stephen Quake said: “It’s an honor to partner with Harvard in building this extraordinary new resource for students and science. This is a once-in-a-generation moment for life sciences and medicine. We are living in such an extraordinary and exciting time for science. Many breakthrough discoveries are going to happen not only broadly but right here on this campus and at this institute.”

CZI’s 10-year vision is to advance research and develop technologies to observe, measure, and analyze any biological process within the human body — across spatial scales and in real time. CZI’s goal is to accelerate scientific progress by funding scientific research to advance entire fields; working closely with scientists and engineers at partner institutions like the Chan Zuckerberg Biohub and Chan Zuckerberg Institute for Advanced Biological Imaging to do the research that can’t be done in conventional environments; and building and democratizing next-generation software and hardware tools to drive biological insights and generate more accurate and biologically important sources of data.

President of Harvard University Lawrence Bacow said: “Here we are with this incredible opportunity that Priscilla Chan and Mark Zuckerberg have given us to imagine taking what we know about the brain, neuroscience and how to model intelligence and putting them together in ways that can inform both, and can truly advance our understanding of intelligence from multiple perspectives.”

Kempner Institute Co-Director and Gordon McKay Professor of Computer Science and of Statistics at the Harvard John A. Paulson School of Engineering and Applied Sciences Sham Kakade said: “Now we begin assembling a world-leading research and educational program at Harvard that collectively tries to understand the fundamental mechanisms of intelligence and seeks to apply these new technologies for the benefit of humanity … We hope to create a vibrant environment for all of us to engage in broader research questions … We want to train the next generation of leaders because those leaders will go on to do the next set of great things.”

Kempner Institute Co-Director and the Alice and Rodman W. Moorhead III Professor of Neurobiology at Harvard Medical School Bernardo Sabatini said: “We’re blending research, education and computation to nurture, raise up and enable any scientist who is interested in unraveling the mysteries of the brain. This field is a nascent and interdisciplinary one, so we’re going to have to teach neuroscience to computational biologists, who are going to have to teach machine learning to cognitive scientists and math to biologists. We’re going to do whatever is necessary to help each individual thrive and push the field forward … Success means we develop mathematical theories that explain how our brains compute and learn, and these theories should be specific enough to be testable and useful enough to start to explain diseases like schizophrenia, dyslexia or autism.”

About the Chan Zuckerberg Initiative

The Chan Zuckerberg Initiative was founded in 2015 to help solve some of society’s toughest challenges — from eradicating disease and improving education, to addressing the needs of our communities. Through collaboration, providing resources and building technology, our mission is to help build a more inclusive, just and healthy future for everyone. For more information, please visit chanzuckerberg.com.

Principled theories, eh. I don’t see a single mention of ethicists or anyone in the social sciences or the humanities or the arts. How are scientists and engineers who have no training in or education in or, even, an introduction to ethics or social impacts or psychology going to manage this?

Mark Zuckerberg’s approach to these issues was something along the lines of “it’s easier to ask for forgiveness than to ask for permission.” I understand there have been changes but it took far too long to recognize the damage let alone attempt to address it.

If you want to gain a little more insight into the Kempner Institute, there’s a December 7, 2021 article by Alvin Powell announcing the institute for the Harvard Gazette,

The institute will be funded by a $500 million gift from Priscilla Chan and Mark Zuckerberg, which was announced Tuesday [December 7, 2021] by the Chan Zuckerberg Initiative. The gift will support 10 new faculty appointments, significant new computing infrastructure, and resources to allow students to flow between labs in pursuit of ideas and knowledge. The institute’s name honors Zuckerberg’s mother, Karen Kempner Zuckerberg, and her parents — Zuckerberg’s grandparents — Sidney and Gertrude Kempner. Chan and Zuckerberg have given generously to Harvard in the past, supporting students, faculty, and researchers in a range of areas, including around public service, literacy, and cures.

“The Kempner Institute at Harvard represents a remarkable opportunity to bring together approaches and expertise in biological and cognitive science with machine learning, statistics, and computer science to make real progress in understanding how the human brain works to improve how we address disease, create new therapies, and advance our understanding of the human body and the world more broadly,” said President Larry Bacow.


Bernardo Sabatini and Sham Kakade [Institute co-directors]

GAZETTE: Tell me about the new institute. What is its main reason for being?

SABATINI: The institute is designed to take from two fields and bring them together, hopefully to create something that’s essentially new, though it’s been tried in a couple of places. Imagine that you have over here cognitive scientists and neurobiologists who study the human brain, including the basic biological mechanisms of intelligence and decision-making. And then over there, you have people from computer science, from mathematics and statistics, who study artificial intelligence systems. Those groups don’t talk to each other very much.

We want to recruit from both populations to fill in the middle and to create a new population, through education, through graduate programs, through funding programs — to grow from academic infancy — those equally versed in neuroscience and in AI systems, who can be leaders for the next generation.

Over the millions of years that vertebrates have been evolving, the human brain has developed specializations that are fundamental for learning and intelligence. We need to know what those are to understand their benefits and to ask whether they can make AI systems better. At the same time, as people who study AI and machine learning (ML) develop mathematical theories as to how those systems work and can say that a network of the following structure with the following properties learns by calculating the following function, then we can take those theories and ask, “Is that actually how the human brain works?”

KAKADE: There’s a question of why now? In the technological space, the advancements are remarkable even to me, as a researcher who knows how these things are being made. I think there’s a long way to go, but many of us feel that this is the right time to study intelligence more broadly. You might also ask: Why is this mission unique and why is this institute different from what’s being done in academia and in industry? Academia is good at putting out ideas. Industry is good at turning ideas into reality. We’re in a bit of a sweet spot. We have the scale to study approaches at a very different level: It’s not going to be just individual labs pursuing their own ideas. We may not be as big as the biggest companies, but we can work on the types of problems that they work on, such as having the compute resources to work on large language models. Industry has exciting research, but the spectrum of ideas produced is very different, because they have different objectives.

For the die-hards, there’s a September 23, 2022 article by Clea Simon in Harvard Gazette, which updates the 2021 story,

Next, Manchester, England.

Manchester Centre for Robotics and AI

Robotots take a break at a lab at The University of Manchester – picture courtesy of Marketing Manchester [downloaded from https://www.manchester.ac.uk/discover/news/manchester-ai-summit-aims-to-attract-experts-in-advanced-engineering-and-robotics/]

A November 22, 2022 University of Manchester press release (also on EurekAlert) announces both a meeting and a new centre, Note: Links to the Centre have been retained; all others have been removed,

How humans and super smart robots will live and work together in the future will be among the key issues being scrutinised by experts at a new centre of excellence for AI and autonomous machines based at The University of Manchester.

The Manchester Centre for Robotics and AI will be a new specialist multi-disciplinary centre to explore developments in smart robotics through the lens of artificial intelligence (AI) and autonomous machinery.

The University of Manchester has built a modern reputation of excellence in AI and robotics, partly based on the legacy of pioneering thought leadership begun in this field in Manchester by legendary codebreaker Alan Turing.

Manchester’s new multi-disciplinary centre is home to world-leading research from across the academic disciplines – and this group will hold its first conference on Wednesday, Nov 23, at the University’s new engineering and materials facilities.

A  highlight will be a joint talk by robotics expert Dr Andy Weightman and theologian Dr Scott Midson which is expected to put a spotlight on ‘posthumanism’, a future world where humans won’t be the only highly intelligent decision-makers.

Dr Weightman, who researches home-based rehabilitation robotics for people with neurological impairment, and Dr Midson, who researches theological and philosophical critiques of posthumanism, will discuss how interdisciplinary research can help with the special challenges of rehabilitation robotics – and, ultimately, what it means to be human “in the face of the promises and challenges of human enhancement through robotic and autonomous machines”.

Other topics that the centre will have a focus on will include applications of robotics in extreme environments.

For the past decade, a specialist Manchester team led by Professor Barry Lennox has designed robots to work safely in nuclear decommissioning sites in the UK. A ground-breaking robot called Lyra that has been developed by Professor Lennox’s team – and recently deployed at the Dounreay site in Scotland, the “world’s deepest nuclear clean up site” – has been listed in Time Magazine’s Top 200 innovations of 2022.

Angelo Cangelosi, Professor of Machine Learning and Robotics at Manchester, said the University offers a world-leading position in the field of autonomous systems – a technology that will be an integral part of our future world. 

Professor Cangelosi, co-Director of Manchester’s Centre for Robotics and AI, said: “We are delighted to host our inaugural conference which will provide a special showcase for our diverse academic expertise to design robotics for a variety of real world applications.

“Our research and innovation team are at the interface between robotics, autonomy and AI – and their knowledge is drawn from across the University’s disciplines, including biological and medical sciences – as well the humanities and even theology. [emphases mine]

“This rich diversity offers Manchester a distinctive approach to designing robots and autonomous systems for real world applications, especially when combined with our novel use of AI-based knowledge.”

Delegates will have a chance to observe a series of robots and autonomous machines being demoed at the new conference.

The University of Manchester’s Centre for Robotics and AI will aim to: 

  • design control systems with a focus on bio-inspired solutions to mechatronics, eg the use of biomimetic sensors, actuators and robot platforms; 
  • develop new software engineering and AI methodologies for verification in autonomous systems, with the aim to design trustworthy autonomous systems; 
  • research human-robot interaction, with a pioneering focus on the use of brain-inspired approaches [emphasis mine] to robot control, learning and interaction; and 
  • research the ethics and human-centred robotics issues, for the understanding of the impact of the use of robots and autonomous systems with individuals and society. 

In some ways, the Kempner Institute and the Manchester Centre for Robotics and AI have very similar interests, especially where the brain is concerned. What fascinates me is the Manchester Centre’s inclusion of theologian Dr Scott Midson and the discussion (at the meeting) of ‘posthumanism’. The difference is between actual engagement at the symposium (the centre) and mere mention in a news release (the institute).

I wish the best for both institutions.

Visualization of RNA structures at near-atomic resolution enabled by nanotechnology

The illustration that accompanies the research is both fascinating and baffling as its caption,

Caption: This illustration is inspired by the Paleolithic rock painting in the Lascaux cave, signifying the acronym of our method, ROCK. Figuratively, the patterns of the rock art in the background (brown) are the 2D projections of the engineered dimeric construct of the Tetrahymena group I intron, while the main object in the front (blue) is the reconstructed 3D cryo-EM map of the dimer, with one monomer in focus and refined to the high resolution that allowed the collaborators to build an atomic model of the RNA. Credit: Wyss Institute at Harvard University

This May 2, 2022 news item on ScienceDaily announces the research into RNA molecules made possible by ROCK (the technology being illustrated in the above),

We live in a world made and run by RNA [ribonucleic acid], the equally important sibling of the genetic molecule DNA. In fact, evolutionary biologists hypothesize that RNA existed and self-replicated even before the appearance of DNA and the proteins encoded by it. Fast forward to modern day humans: science has revealed that less than 3% of the human genome is transcribed into messenger RNA (mRNA) molecules that in turn are translated into proteins. In contrast, 82% of it is transcribed into RNA molecules with other functions many of which still remain enigmatic.

To understand what an individual RNA molecule does, its 3D structure needs to be deciphered at the level of its constituent atoms and molecular bonds. Researchers have routinely studied DNA and protein molecules by turning them into regularly packed crystals that can be examined with an X-ray beam (X-ray crystallography) or radio waves (nuclear magnetic resonance). However, these techniques cannot be applied to RNA molecules with nearly the same effectiveness because their molecular composition and structural flexibility prevent them from easily forming crystals.

Now, a research collaboration led by Wyss Core Faculty member Peng Yin, Ph.D. at the Wyss Institute for Biologically Inspired Engineering at Harvard University, and Maofu Liao, Ph.D. at Harvard Medical School (HMS), has reported a fundamentally new approach to the structural investigation of RNA molecules. ROCK, as it is called, uses an RNA nanotechnological technique that allows it to assemble multiple identical RNA molecules into a highly organized structure, which significantly reduces the flexibility of individual RNA molecules and multiplies their molecular weight. Applied to well-known model RNAs with different sizes and functions as benchmarks, the team showed that their method enables the structural analysis of the contained RNA subunits with a technique known as cryo-electron microscopy (cryo-EM). Their advance is reported in Nature Methods.

A May 2, 2022 Wyss Institute for Biologically Inspired Engineering at Harvard University news release (also on EurekAlert) by Benjamin Boettner, which originated the news item, delves further into the imaging technology, Note: Links have been removed,

“ROCK is breaking the current limits of RNA structural investigations and enables 3D structures of RNA molecules to be unlocked that are difficult or impossible to access with existing methods, and at near-atomic resolution,” said Yin, who together with Liao led the study. “We expect this advance to invigorate many areas of fundamental research and drug development, including the burgeoning field of RNA therapeutics.” Yin also is a leader of the Wyss Institute’s Molecular Robotics Initiative and Professor in the Department of Systems Biology at HMS.

Gaining control over RNA

Yin’s team at the Wyss Institute has pioneered various approaches that enable DNA and RNA molecules to self-assemble into large structures based on different principles and requirements, including DNA bricks and DNA origami. They hypothesized that such strategies could also be used to assemble naturally occurring RNA molecules into highly ordered circular complexes in which their freedom to flex and move is highly restricted by specifically linking them together. Many RNAs fold in complex yet predictable ways, with small segments base-pairing with each other. The result often is a stabilized “core” and “stem-loops” bulging out into the periphery. 

“In our approach we install ‘kissing loops’ that link different peripheral stem-loops belonging to two copies of an identical RNA in a way that allows a overall stabilized ring to be formed, containing multiple copies of the RNA of interest,” said Di Liu, Ph.D., one of two first-authors and a Postdoctoral Fellow in Yin’s group. “We speculated that these higher-order rings could be analyzed with high resolution by cryo-EM, which had been applied to RNA molecules with first success.”

Picturing stabilized RNA

In cryo-EM, many single particles are flash-frozen at cryogenic temperatures to prevent any further movements, and then visualized with an electron microscope and the help of computational algorithms that compare the various aspects of a particle’s 2D surface projections and reconstruct its 3D architecture. Peng and Liu teamed up with Liao and his former graduate student François Thélot, Ph.D., the other co-first author of the study. Liao with his group has made important contributions to the rapidly advancing cryo-EM field and the experimental and computational analysis of single particles formed by specific proteins.

“Cryo-EM has great advantages over traditional methods in seeing high-resolution details of biological molecules including proteins, DNAs and RNAs, but the small size and moving tendency of most RNAs prevent successful determination of RNA structures. Our novel method of assembling RNA multimers solves these two problems at the same time, by increasing the size of RNA and reducing its movement,” said Liao, who also is Associate Professor of Cell Biology at HMS. “Our approach has opened the door to rapid structure determination of many RNAs by cryo-EM.” The integration of RNA nanotechnology and cryo-EM approaches led the team to name their method “RNA oligomerization-enabled cryo-EM via installing kissing loops” (ROCK).

To provide proof-of-principle for ROCK, the team focused on a large intron RNA from Tetrahymena, a single-celled organism, and a small intron RNA from Azoarcus, a nitrogen-fixing bacterium, as well as the so-called FMN riboswitch. Intron RNAs are non-coding RNA sequences scattered throughout the sequences of freshly-transcribed RNAs and have to be “spliced” out in order for the mature RNA to be generated. The FMN riboswitch is found in bacterial RNAs involved in the biosynthesis of flavin metabolites derived from vitamin B2. Upon binding one of them, flavin mononucleotide (FMN), it switches its 3D conformation and suppresses the synthesis of its mother RNA.  

“The assembly of the Tetrahymena group I intron into a ring-like structure made the samples more homogenous, and enabled the use of computational tools leveraging the symmetry of the assembled structure. While our dataset is relatively modest in size, ROCK’s innate advantages allowed us to resolve the structure at an unprecedented resolution,” said Thélot. “The RNA’s core is resolved at 2.85 Å [one Ångström is one ten-billions (US) of a meter and the preferred metric used by structural biologists], revealing detailed features of the nucleotide bases and sugar backbone. I don’t think we could have gotten there without ROCK – or at least not without considerably more resources.” 

Cryo-EM also is able to capture molecules in different states if they, for example, change their 3D conformation as part of their function. Applying ROCK to the Azoarcus intron RNA and the FMN riboswitch, the team managed to identify the different conformations that the Azoarcus intron transitions through during its self-splicing process, and to reveal the relative conformational rigidity of the ligand-binding site of the FMN riboswitch.

“This study by Peng Yin and his collaborators elegantly shows how RNA nanotechnology can work as an accelerator to advance other disciplines. Being able to visualize and understand the structures of many naturally occurring RNA molecules could have tremendous impact on our understanding of many biological and pathological processes across different cell types, tissues, and organisms, and even enable new drug development approaches,” said Wyss Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.

The study was also authored by Joseph Piccirilli, Ph.D., an expert in RNA chemistry and biochemistry and Professor at The University of Chicago. It was supported by the National Science Foundation (NSF; grant# CMMI-1333215, CCMI-1344915, and CBET-1729397), Air Force Office of Scientific Research (AFOSR; grant MURI FATE, #FA9550-15-1-0514), National Institutes of Health (NIH; grant# 5DP1GM133052, R01GM122797, and R01GM102489), and the Wyss Institute’s Molecular Robotics Initiative.

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

Sub-3-Å cryo-EM structure of RNA enabled by engineered homomeric self-assembly by Di Liu, François A. Thélot, Joseph A. Piccirilli, Maofu Liao & Peng Yin. Nature Methods (2022) DOI: https://doi.org/10.1038/s41592-022-01455-w Published: 02 May 2022

This paper is behind a paywall.

Physics of a singing saw could lead to applications in sensing, nanoelectronics, photonics, etc.

I’d forgotten how haunting a musical saw can sound,

An April 22, 2022 news item on Nanowerk announces research into the possibilities of a singing saw,

The eerie, ethereal sound of the singing saw has been a part of folk music traditions around the globe, from China to Appalachia, since the proliferation of cheap, flexible steel in the early 19th century. Made from bending a metal hand saw and bowing it like a cello, the instrument reached its heyday on the vaudeville stages of the early 20th century and has seen a resurgence thanks, in part, to social media.

As it turns out, the unique mathematical physics of the singing saw may hold the key to designing high quality resonators for a range of applications.

In a new paper, a team of researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Department of Physics used the singing saw to demonstrate how the geometry of a curved sheet, like curved metal, could be tuned to create high-quality, long-lasting oscillations for applications in sensing, nanoelectronics, photonics and more.

An April 21, 2022 Harvard University John A. Paulson School of Engineering and Applied Sciences (SEAS) news release by Leah Burrows (also on EurekAlert but published on April 22, 2022) delves further into physics of singing saws,

“Our research offers a robust principle to design high-quality resonators independent of scale and material, from macroscopic musical instruments to nanoscale devices, simply through a combination of geometry and topology,” said L Mahadevan, the Lola England de Valpine Professor of Applied Mathematics, of Organismic and Evolutionary Biology, and of Physics and senior author of the study.

While all musical instruments are acoustic resonators of a kind, none work quite like the singing saw.

“How the singing saw sings is based on a surprising effect,” said Petur Bryde, a graduate student at SEAS and co-first author of the paper. “When you strike a flat elastic sheet, such as a sheet of metal, the entire structure vibrates. The energy is quickly lost through the boundary where it is held, resulting in a dull sound that dissipates quickly. The same result is observed if you curve it into a J-shape. But, if you bend the sheet into an S-shape, you can make it vibrate in a very small area, which produces a clear, long-lasting tone.”

The geometry of the curved saw creates what musicians call the sweet spot and what physicists call localized vibrational modes — a confined area on the sheet which resonates without losing energy at the edges.

Importantly, the specific geometry of the S-curve doesn’t matter. It could be an S with a big curve at the top and a small curve at the bottom or visa versa. 

“Musicians and researchers have known about this robust effect of geometry for some time, but the underlying mechanisms have remained a mystery,” said Suraj Shankar, a Harvard Junior Fellow in Physics and SEAS and co-first author of the study.  “We found a mathematical argument that explains how and why this robust effect exists with any shape within this class, so that the details of the shape are unimportant, and the only fact that matters is that there is a reversal of curvature along the saw.”

Shankar, Bryde and Mahadevan found that explanation via an analogy to very different class of physical systems — topological insulators. Most often associated with quantum physics, topological insulators are materials that conduct electricity in their surface or edge but not in the middle and no matter how you cut these materials, they will always conduct on their edges.

“In this work, we drew a mathematical analogy between the acoustics of bent sheets and these quantum and electronic systems,” said Shankar.

By using the mathematics of topological systems, the researchers found that the localized vibrational modes in the sweet spot of singing saw were governed by a topological parameter that can be computed and which relies on nothing more than the existence of two opposite curves in the material. The sweet spot then behaves like an internal “edge” in the saw.

“By using experiments, theoretical and numerical analysis, we showed that the S-curvature in a thin shell can localize topologically-protected modes at the ‘sweet spot’ or inflection line, similar to exotic edge states in topological insulators,” said Bryde. “This phenomenon is material independent, meaning it will appear in steel, glass or even graphene.”

The researchers also found that they could tune the localization of the mode by changing the shape of the S-curve, which is important in applications such as sensing, where you need a resonator that is tuned to very specific frequencies.

Next, the researchers aim to explore localized modes in doubly curved structures, such as bells and other shapes.

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

Geometric control of topological dynamics in a singing saw by Suraj Shankar, Petur Bryde, and L. Mahadevan. The Proceedings of the National Academy of Sciences (PNAS) April 21, 2022 | 119 (17) e2117241119 DOI: https://doi.org/10.1073/pnas.2117241119

This paper is open (free) access.

Ancient Namibian gemstone could be key to new light-based quantum computers

Researchers in Scotland, the US, Australia, and Denmark have a found a solution to a problem with creating light-based computers according to an April 15, 2022 news item on phys.org,

A special form of light made using an ancient Namibian gemstone could be the key to new light-based quantum computers, which could solve long-held scientific mysteries, according to new research led by the University of St Andrews.

The research, conducted in collaboration with scientists at Harvard University in the US, Macquarie University in Australia and Aarhus University in Denmark and published in Nature Materials, used a naturally mined cuprous oxide (Cu2O) gemstone from Namibia to produce Rydberg polaritons, the largest hybrid particles of light and matter ever created.

Cuprous oxide – the mined crystal from Namibia used for making Rydberg polaritons. Courtesy: University of St. Andrews

An April 15, 2022 University of St. Andrews press release, which originated the news item, describes Rydberg polaritons and explains why they could be the key to light-based quantum computing,

Rydberg polaritons switch continually from light to matter and back again. In Rydberg polaritons, light and matter are like two sides of a coin, and the matter side is what makes polaritons interact with each other.

This interaction is crucial because this is what allows the creation of quantum simulators, a special type of quantum computer, where information is stored in quantum bits. These quantum bits [qubits], unlike the binary bits in classical computers that can only be 0 or 1, can take any value between 0 and 1. They can therefore store much more information and perform several processes simultaneously.

This capability could allow quantum simulators to solve important mysteries of physics, chemistry and biology, for example, how to make high-temperature superconductors for highspeed trains, how cheaper fertilisers could be made potentially solving global hunger, or how proteins fold making it easier to produce more effective drugs.

Project lead Dr Hamid Ohadi, of the School of Physics and Astronomy at the University of St Andrews, said: “Making a quantum simulator with light is the holy grail of science. We have taken a huge leap towards this by creating Rydberg polaritons, the key ingredient of it.”

To create Rydberg polaritons, the researchers trapped light between two highly reflective mirrors. A cuprous oxide crystal from a stone mined in Namibia was then thinned and polished to a 30-micrometer thick slab (thinner than a strand of human hair) and sandwiched between the two mirrors to make Rydberg polaritons 100 times larger than ever demonstrated before.

One of the leading authors Dr Sai Kiran Rajendran, of the School of Physics and Astronomy at the University of St Andrews, said: “Purchasing the stone on eBay was easy. The challenge was to make Rydberg polaritons that exist in an extremely narrow colour range.”

The team is currently further refining these methods in order to explore the possibility of making quantum circuits, which are the next ingredient for quantum simulators.

The research was funded by UK Engineering and Physical Sciences Research Council (EPSRC).

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

Rydberg exciton–polaritons in a Cu2O microcavity by Konstantinos Orfanakis, Sai Kiran Rajendran, Valentin Walther, Thomas Volz, Thomas Pohl & Hamid Ohadi. Nature Materials (2022) DOI: DOIhttps://doi.org/10.1038/s41563-022-01230-4 Published: 14 April 2022

This paper is behind a paywall.

Xenobots (living robots) that can reproduce

Xenobots (living robots made from African frog (Xenopus laevis) frog cells) can now self-replicate. First mentioned here in a June 21, 2021 posting, xenobots have captured the imagination of various media outlets including the Canadian Broadcasting Corporation’s (CBC) Quirks and Quarks radio programme and blog where Amanda Buckiewicz posted a December 3, 2021 article about the latest xenobot development (Note: Links have been removed),

In a new study, Bongard [Joshua Bongard, a computer scientist at the University of Vermont] and his colleagues from Tufts University and Harvard’s Wyss Institute for Biologically Inspired Engineering found that the xenobots would autonomously collect loose single cells in their environment, gathering hundreds of cells together until new xenobots had formed.

“This took a little bit for us to wrap our minds around,” he said. “There’s no programming here. Instead, we’re designing or shaping these xenobots, and what they do, the way they behave, is based on shape.”

“We take a couple of thousand of those frog cells and we squish them together into a ball and put that in the bottom of a petri dish,” Bongard told Quirks & Quarks host Bob McDonald. 

“If you were to look into the dish, you would see some very small, what look like specks of pepper, moving about in the bottom of the petri dish.”

The xenobots initially received no instruction from humans on how to replicate. But when researchers added extra cells to the dish containing xenobots, they observed that the xenobots would assemble them into piles.

“Cells early in development are sticky,” said Bongard. “If the pile is large enough and the cells stick together, the outer ones on the surface will grow very small hairs, which are called cilia. And eventually, after four days, those cilia will start to beat back and forth like flexible oars, and the pile will start moving.”

“And that’s a child xenobot.” 

A November 29, 2021 Wyss Institute news release by Joshua Brown describes the process a little differently,

To persist, life must reproduce. Over billions of years, organisms have evolved many ways of replicating, from budding plants to sexual animals to invading viruses.

Now scientists at the University of Vermont, Tufts University, and the Wyss Institute for Biologically Inspired Engineering at Harvard University have discovered an entirely new form of biological reproduction—and applied their discovery to create the first-ever, self-replicating living robots.

The same team that built the first living robots (“Xenobots,” assembled from frog cells—reported in 2020) has discovered that these computer-designed and hand-assembled organisms can swim out into their tiny dish, find single cells, gather hundreds of them together, and assemble “baby” Xenobots inside their Pac-Man-shaped “mouth”—that, a few days later, become new Xenobots that look and move just like themselves.

And then these new Xenobots can go out, find cells, and build copies of themselves. Again and again.

In a Xenopus laevis frog, these embryonic cells would develop into skin. “They would be sitting on the outside of a tadpole, keeping out pathogens and redistributing mucus,” says Michael Levin, Ph.D., a professor of biology and director of the Allen Discovery Center at Tufts University and co-leader of the new research. “But we’re putting them into a novel context. We’re giving them a chance to reimagine their multicellularity.” Levin is also an Associate Faculty member at the Wyss Institute.

And what they imagine is something far different than skin. “People have thought for quite a long time that we’ve worked out all the ways that life can reproduce or replicate. But this is something that’s never been observed before,” says co-author Douglas Blackiston, Ph.D., the senior scientist at Tufts University and the Wyss Institute who assembled the Xenobot “parents” and developed the biological portion of the new study.

“This is profound,” says Levin. “These cells have the genome of a frog, but, freed from becoming tadpoles, they use their collective intelligence, a plasticity, to do something astounding.” In earlier experiments, the scientists were amazed that Xenobots could be designed to achieve simple tasks. Now they are stunned that these biological objects—a computer-designed collection of cells—will spontaneously replicate. “We have the full, unaltered frog genome,” says Levin, “but it gave no hint that these cells can work together on this new task,” of gathering and then compressing separated cells into working self-copies.

“These are frog cells replicating in a way that is very different from how frogs do it. No animal or plant known to science replicates in this way,” says Sam Kriegman, Ph.D.,  the lead author on the new study, who completed his Ph.D. in Bongard’s lab at UVM and is now a post-doctoral researcher at Tuft’s Allen Center and Harvard University’s Wyss Institute for Biologically Inspired Engineering.

Both Buckiewicz’s December 3, 2021 article and Brown’s November 29, 2021 Wyss Institute news release are good reads with liberal used of embedded images. If you have time, start with Buckiewicz as she provides a good introduction and follow up with Brown who gives more detail and has an embedded video of a December 1, 2021 panel discussion with the scientists behind the xenobots.

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

Kinematic self-replication in reconfigurable organisms by Sam Kriegman, Douglas Blackiston, Michael Levin, and Josh Bongard. PNAS [Proceedings of the National Academy of Sciences] December 7, 2021 118 (49) e2112672118; https://doi.org/10.1073/pnas.2112672118

This paper appears to be open access.

Cellulose nanocrystals (CNC), protein, and starch eletrospun to develop ‘smart’ food packaging

A December 29, 2021 news item on ScienceDaily announces research into ;smart’ sustainable packaging from a joint Nanyang Technical University and Harvard University,

A team of scientists from Nanyang Technological University, Singapore (NTU Singapore) and Harvard T.H. Chan School of Public Health, US, has developed a ‘smart’ food packaging material that is biodegradable, sustainable and kills microbes that are harmful to humans. It could also extend the shelf-life of fresh fruit by two to three days.

The waterproof food packaging is made from a type of corn protein called zein, starch and other naturally derived biopolymers, infused with a cocktail of natural antimicrobial compounds. These include oil from thyme, a common herb used in cooking, and citric acid, which is commonly found in citrus fruits.

A December 28, 2021 Nanyang Technological University press release (PDF), also on EurekAlert but published December 27, 2021, which originated the news item, offers a few more details about the research (Note 1: Links have been removed; Note 2: I had to dig into the abstract to find the cellulose nanocrystals),

In lab experiments, when exposed to an increase in humidity or enzymes from harmful bacteria, the fibres in the packaging have been shown to release the natural antimicrobial compounds, killing common dangerous bacteria that contaminate food, such as E. Coli and Listeria, as well as fungi.

The packaging is designed to release the necessary miniscule amounts of antimicrobial compounds only in response to the presence of additional humidity or bacteria. This ensures that the packaging can endure several exposures, and last for months.

As the compounds combat any bacteria that grow on the surface of the packaging as well as on the food product itself, it has the potential to be used for a large variety of products, including ready-to-eat foods, raw meat, fruits, and vegetables.

In an experiment, strawberries that were wrapped in the packaging stayed fresh for seven days before developing mould, compared to counterparts that were kept in mainstream fruit plastic boxes, which only stayed fresh for four days.

The invention is the result of the collaboration by scientists from the NTU-Harvard T. H. Chan School of Public Health Initiative for Sustainable Nanotechnology (NTU-Harvard SusNano), which brings together NTU and Harvard Chan School researchers to work on cutting edge applications in agriculture and food, with an emphasis on developing non-toxic and environmentally safe nanomaterials.

The development of this advanced food packaging material is part of the University’s efforts to promote sustainable food tech solutions, that is aligned with the NTU 2025 strategic plan, which aims to develop sustainable solutions to address some of humanity’s pressing grand challenges.

Professor Mary Chan, Director of NTU’s Centre of Antimicrobial Bioengineering, who co-led the project, said: “This invention would serve as a better option for packaging in the food industry, as it has demonstrated superior antimicrobial qualities in combatting a myriad of food-related bacteria and fungi that could be harmful to humans. The packaging can be applied to various produces such as fish, meat, vegetables, and fruits. The smart release of antimicrobials only when bacteria or high humidity is present, provides protection only when needed thus minimising the use of chemicals and preserving the natural composition of foods packaged.”

Professor Philip Demokritou, Adjunct Professor of Environmental Health at Harvard Chan School, who is also Director of Nanotechnology and Nanotoxicology Center and Co-director of NTU-Harvard Initiative on Sustainable Nanotechnology, who co-led the study, said: “Food safety and waste have become a major societal challenge of our times with immense public health and economic impact which compromises food security. One of the most efficient ways to enhance food safety and reduce spoilage and waste is to develop efficient biodegradable non-toxic food packaging materials. In this study, we used nature-derived compounds including biopolymers, non-toxic solvents, and nature-inspired antimicrobials and develop scalable systems to synthesise smart antimicrobial materials which can be used not only to enhance food safety and quality but also to eliminate the harm to the environment and health and reduce the use of non-biodegradable plastics at global level and promote sustainable agri-food systems.” 

Providing an independent assessment of the work done by the NTU research team, Mr Peter Barber, CEO of ComCrop, a Singapore company that pioneered urban rooftop farming, said: “The NTU-Harvard Chan School food packaging material would serve as a sustainable solution for companies like us who want to cut down on the usage of plastic and embrace greener alternatives. As ComCrop looks to ramp up product to boost Singapore’s food production capabilities, the volume of packaging we need will increase in sync, and switching to a material such as this would help us have double the impact. The wrapping’s antimicrobial properties, which could potentially extend the shelf life of our vegetables, would serve us well. The packaging material holds promise to the industry, and we look forward to learning more about the wrapping and possibly adopting it for our usage someday.”

The results of the study were published in the peer-reviewed academic journal ACS Applied Materials & Interfacesin October [2021].

Cutting down on packaging waste

The packaging industry is the largest and growing consumer of synthetic plastics derived from fossil fuels, with food packaging plastics accounting for the bulk of plastic waste that are polluting the environment.

In Singapore, packaging is a major source of trash, with data from Singapore’s National Environment Agency showing that out of the 1.76 million tonnes of waste disposed of by domestic sources in 2018, one third of it was packaging waste, and over half of it (55 per cent) was plastic.

The smart food package material, when scaled up, could serve as an alternative to cut down on the amount of plastic waste, as it is biodegradable. Its main ingredient, zein, is also produced from corn gluten meal, which is a waste by-product from using corn starch or oils in order to produce ethanol.

The food packaging material is produced by electrospinning[1] the zein, the antimicrobial compounds with cellulose, a natural polymer starch that makes up plant cell walls, and acetic acid, which is commonly found in vinegar.

Prof Mary Chan added: “The sustainable and biodegradable active food packaging, which has inbuilt technology to keep bacteria and fungus at bay, is of great importance to the food industry. It could serve as an environmentally friendly alternative to petroleum-based polymers used in commercial food packaging, such as plastic, which have a significant negative environmental impact.”

Prof Demokritou added: “Due to the globalisation of food supply and attitude shift towards a healthier lifestyle and environmentally friendly food packaging, there is a need to develop biodegradable, non-toxic and smart/responsive materials to enhance food safety and quality. Development of scalable synthesis platforms for developing food packaging materials that are composed of nature derived, biodegradable biopolymers and nature inspired antimicrobials, coupled with stimuli triggered approaches will meet the emerging societal needs to reduce food waste and enhance food safety and quality.”

The team of NTU and Harvard Chan School researchers hope to scale up their technology with an industrial partner, with the aim of commercialisation within the next few years.

They are also currently working on developing other technologies to develop biopolymer-based smart food package materials to enhance food safety and quality.

Here’s a link to and a citation for the paper, followed by the key (nanocellulose crystal mention) sentences in the abstract,

Enzyme- and Relative Humidity-Responsive Antimicrobial Fibers for Active Food Packaging by Zeynep Aytac, Jie Xu, Suresh Kumar Raman Pillai, Brian D. Eitzer, Tao Xu, Nachiket Vaze, Kee Woei Ng, Jason C. White, Mary B. Chan-Park, Yaguang Luo, and Philip Demokritou. ACS Appl. Mater. Interfaces 2021, 13, 42, 50298–50308 I: https://doi.org/10.1021/acsami.1c12319 Publication Date: October 14, 2021 Copyright © 2021 American Chemical Society

This paper is behind a paywall.

Excerpt from abstract,

Active food packaging materials that are sustainable, biodegradable, and capable of precise delivery of antimicrobial active ingredients (AIs) are in high demand. Here, we report the development of novel enzyme- and relative humidity (RH)-responsive antimicrobial fibers with an average diameter of 225 ± 50 nm, which can be deposited as a functional layer for packaging materials. Cellulose nanocrystals (CNCs) [emphasis mine], zein (protein), and starch were electrospun to form multistimuli-responsive fibers that incorporated a cocktail of both free nature-derived antimicrobials such as thyme oil, citric acid, and nisin and cyclodextrin-inclusion complexes (CD-ICs) of thyme oil, sorbic acid, and nisin. …

I have been following the CNC story for some time. If you’re curious, just use ‘cellulose nanocrystal(s)’ as your search term. You can find out more about ComCrop here.