3 Questions: Wiebke Denecke on a landmark project for Chinese literature

Nuns writing fine poetry. Centuries-old joke books. An epic travelogue ending with a visit to Genghis Khan. These are just a few things readers can experience through the new Hsu-Tang Library of Classical Chinese Literature, published by Oxford University Press.

The series is modeled on the Loeb Classical Library, which debuted in 1912 and features about 500 titles of Greek and Roman literature, in their distinctive red and green covers. The Hsu-Tang Library of Classical Chinese Literature series is starting with five titles, under the supervision of founding editor-in-chief Wiebke Denecke, the S. C. Fang Professor of Chinese Language and Culture in MIT’s literature section. The aim is to bring these classic texts, from the first millennium BCE through the early 20th century, to the world, in engaging bilingual editions. There will be four more new titles next year, with dozens lined up after that.

The series benefactors are Oscar Liu-Chien Tang and Agnes Hsin Mei Hsu-Tang, whose family has also been MIT benefactors and has a notable record of philanthropy for institutions and programs in the arts, humanities, and education. MIT News talked with Denecke about the ambitious new book series.

Q: What is the Hsu-Tang Library of Classical Chinese Literature?

A: This is a library of classical Chinese literature, covering three millennia, from what is now China and from many other places. Just as Latin was the lingua franca in Europe, classical Chinese was the lingua franca of writers in East Asia, so we include authors from Japan, Korea, and Vietnam. The editions are bilingual, Chinese on one side of the page and English on the other.

It belongs to a certain type of project that you could call endowed bilingual libraries. This started 100 years ago with the Loeb Classical Library of classic Greco-Roman literature. A decade ago, the Murty Classical Library of India was launched, and now here we have a new library of classical Chinese literature. It is a great moment for world literature.

We publish translations that are both solidly scholarly and eminently readable. Our associate editor is Lucas Klein, who has a vision of literary magic that makes words sparkle — it’s something he has really emphasized.

Our donors, Agnes Hsin Mei Hsu-Tang and Oscar Liu-Chien Tang, are particularly interesting. Agnes Hsu-Tang is the descendant of Xu Guangqi, who was co-translator with Matteo Ricci, an Italian Jesuit missionary in the 17th century, of Euclid’s “Elements.” Agnes has another great ancestor, Ji Yun, who compiled one of the greatest encyclopedias of the world, in the 18th century. It’s not just somebody from the Chinese world supporting this, but there’s a family lineage of translating knowledge onto a global stage, a symbol of East-West cultural exchange.

Q: What can we discover, or rediscover, about Chinese-language literature through this library?

A: I think it’s an important moment for the humanities generally. The Loeb Library was established when James Loeb himself said the humanities were being neglected more than at any time since perhaps the Middle Ages. Overall, we have a three-pronged strategy: First, we try to make the canonical new. Then we go beyond what anglophone readers might have heard about Chinese literature. For instance, we have three joke collections, in “The Misadventures of Master Mugwort.” In China, joke collections were very popular, and there’s a lot of political satire in there. But there is a common prejudice that China lacks satirical literature. Third, the series emphasizes that there is more than 2,000 years of common cultural heritage in East Asia. That’s a real message right there.

We publish works that are very surprising, such as “An Anthology of Poetry by Buddhist Nuns of Late Imperial China.” Many of these are first translations. We wanted a voice of the female experience, often in very precarious times. Some nuns were from elite ranks and had lost their husbands. Others were orphaned. It’s a real archaeology of female voices.

It's a very good antidote to the idea that nuns were confined. Quite to the contrary, they made relationships they never could have in a household. They were writing poetry and painting, and it’s very empowering. One such example is Shangjian Huizong’s 17^th-century poem, “Village Life.” Her husband died in prison, and she wrote three volumes of poetry, including these lines:

“Living here impoverished / I’ve lost all taste for ornaments … / The face of the woman in my mirror / is a flower that knows emptiness”

So what is amazing here? Obviously as a nun she was impoverished. The ornaments are hair ornaments, and it goes with a literary tradition in China to write about women in a boudoir — usually written by males, but here the boudoir implies self-reflectivity. The flower is a natural ornament; it also knows that emptiness accompanies the idea of enlightenment, in the Buddhist sense. So, she turns around boudoir imagery, saying she realizes in the symbolic mirror that she has gained enlightenment. These lines have incredible literary value.

Q: Another one of the first five volumes is “Daoist Master Changchun’s Journey to the West,” a firsthand account of a visit to Genghis Khan by a Chinese traveling party on a long diplomatic trip. Surely there are not many texts like this. What is it about?

A: This is written by a disciple of a Daoist patriarch who was summoned by Genghis Khan in the 1220s, when the Mongols were rushing through the continent. They basically emerged from nowhere, didn’t have a lot of history or writing behind them, and shaped world history. There are so few eyewitness sources, it’s amazing to have a travelogue with so much detail. It’s also made special by all the poetry in it, which in the Chinese tradition was always the main medium of experiencing reality and expressing it.

In this text, poetry becomes a way to cope with this travel experience: You start in China, go to Central Asia, like to the city of Samarkind, and encounter different people, different plants, Islam, sweet melons, and people drinking from glass vessels never seen in China. It’s a way to familiarize and exoticize at the same time. And the writer observes a person — we know today it’s a muezzin — lead in “petitioning heaven” for the Muslim prayer. This is an encounter with Islam, though he doesn’t have a real concept of that.

On the other hand, Genghis Khan is intensely interested in the Dao — or at least that’s how it’s depicted. The first three times they meet, the conversation is always about the Dao. The Chinese want to believe the other side is interested in them. Finally, this is also hagiographic text, a sacred eulogy of this patriarch, and it’s a process of getting political capital out of the connections with Genghis Khan.

Through all of this, we are really trying to develop what we call the Hsu-Tang Library style: smartly scholarly, where you feel there’s something gained in translation.

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A mineral produced by plate tectonics has a global cooling effect, study finds

MIT geologists have found that a clay mineral on the seafloor, called smectite, has a surprisingly powerful ability to sequester carbon over millions of years.

Under a microscope, a single grain of the clay resembles the folds of an accordion. These folds are known to be effective traps for organic carbon.

Now, the MIT team has shown that the carbon-trapping clays are a product of plate tectonics: When oceanic crust crushes against a continental plate, it can bring rocks to the surface that, over time, can weather into minerals including smectite. Eventually, the clay sediment settles back in the ocean, where the minerals trap bits of dead organisms in their microscopic folds. This keeps the organic carbon from being consumed by microbes and expelled back into the atmosphere as carbon dioxide.

Over millions of years, smectite can have a global effect, helping to cool the entire planet. Through a series of analyses, the researchers showed that smectite was likely produced after several major tectonic events over the last 500 million years. During each tectonic event, the clays trapped enough carbon to cool the Earth and induce the subsequent ice age.

The findings are the first to show that plate tectonics can trigger ice ages through the production of carbon-trapping smectite.

These clays can be found in certain tectonically active regions today, and the scientists believe that smectite continues to sequester carbon, providing a natural, albeit slow-acting, buffer against humans’ climate-warming activities.

“The influence of these unassuming clay minerals has wide-ranging implications for the habitability of planets,” says Joshua Murray, a graduate student in MIT’s Department of Earth, Atmospheric, and Planetary Sciences. “There may even be a modern application for these clays in offsetting some of the carbon that humanity has placed into the atmosphere.”

Murray and Oliver Jagoutz, professor of geology at MIT, have published their findings today in Nature Geoscience.

A clear and present clay

The new study follows up on the team’s previous work, which showed that each of the Earth’s major ice ages was likely triggered by a tectonic event in the tropics. The researchers found that each of these tectonic events exposed ocean rocks called ophiolites to the atmosphere. They put forth the idea that, when a tectonic collision occurs in a tropical region, ophiolites can undergo certain weathering effects, such as exposure to wind, rain, and chemical interactions, that transform the rocks into various minerals, including clays.

“Those clay minerals, depending on the kinds you create, influence the climate in different ways,” Murray explains.

At the time, it was unclear which minerals could come out of this weathering effect, and whether and how these minerals could directly contribute to cooling the planet. So, while it appeared there was a link between plate tectonics and ice ages, the exact mechanism by which one could trigger the other was still in question.

With the new study, the team looked to see whether their proposed tectonic tropical weathering process would produce carbon-trapping minerals, and in quantities that would be sufficient to trigger a global ice age.

The team first looked through the geologic literature and compiled data on the ways in which major magmatic minerals weather over time, and on the types of clay minerals this weathering can produce. They then worked these measurements into a weathering simulation of different rock types that are known to be exposed in tectonic collisions.

“Then we look at what happens to these rock types when they break down due to weathering and the influence of a tropical environment, and what minerals form as a result,” Jagoutz says.

Next, they plugged each weathered, “end-product” mineral into a simulation of the Earth’s carbon cycle to see what effect a given mineral might have, either in interacting with organic carbon, such as bits of dead organisms, or with inorganic, in the form of carbon dioxide in the atmosphere.

From these analyses, one mineral had a clear presence and effect: smectite. Not only was the clay a naturally weathered product of tropical tectonics, it was also highly effective at trapping organic carbon. In theory, smectite seemed like a solid connection between tectonics and ice ages.

But were enough of the clays actually present to trigger the previous four ice ages? Ideally, researchers should confirm this by finding smectite in ancient rock layers dating back to each global cooling period.

“Unfortunately, as clays are buried by other sediments, they get cooked a bit, so we can’t measure them directly,” Murray says. “But we can look for their fingerprints.”

A slow build

The team reasoned that, as smectites are a product of ophiolites, these ocean rocks also bear characteristic elements such as nickel and chromium, which would be preserved in ancient sediments. If smectites were present in the past, nickel and chromium should be as well.

To test this idea, the team looked through a database containing thousands of oceanic sedimentary rocks that were deposited over the last 500 million years. Over this time period, the Earth experienced four separate ice ages. Looking at rocks around each of these periods, the researchers observed large spikes of nickel and chromium, and inferred from this that smectite must also have been present.

By their estimates, the clay mineral could have increased the preservation of organic carbon by less than one-tenth of a percent. In absolute terms, this is a miniscule amount. But over millions of years, they calculated that the clay’s accumulated, sequestered carbon was enough to trigger each of the four major ice ages.

“We found that you really don’t need much of this material to have a huge effect on the climate,” Jagoutz says.

“These clays also have probably contributed some of the Earth’s cooling in the last 3 to 5 million years, before humans got involved,” Murray adds. “In the absence of humans, these clays are probably making a difference to the climate. It’s just such a slow process.”

“Jagoutz and Murray’s work is a nice demonstration of how important it is to consider all biotic and physical components of the global carbon cycle,” says Lee Kump, a professor of geosciences at Penn State University, who was not involved with the study. “Feedbacks among all these components control atmospheric greenhouse gas concentrations on all time scales, from the annual rise and fall of atmospheric carbon dioxide levels to the swings from icehouse to greenhouse over millions of years.”

Could smectites be harnessed intentionally to further bring down the world’s carbon emissions? Murray sees some potential, for instance to shore up carbon reservoirs such as regions of permafrost. Warming temperatures are predicted to melt permafrost and expose long-buried organic carbon. If smectites could be applied to these regions, the clays could prevent this exposed carbon from escaping into and further warming the atmosphere.

“If you want to understand how nature works, you have to understand it on the mineral and grain scale,” Jagoutz says. “And this is also the way forward for us to find solutions for this climatic catastrophe. If you study these natural processes, there’s a good chance you will stumble on something that will be actually useful.”

This research was funded, in part, by the National Science Foundation.

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Immune action at a distance

For most metastatic cancer types, there are no reliably effective treatments. Therapies may slow the growth of tumors, but they will not eradicate them. Occasionally, however, treating a tumor in one location will cause untreated tumors elsewhere in the body to shrink or even regress completely — a dramatic but exceedingly rare phenomenon known as the abscopal effect.

Cancer researchers have sought methods to induce the abscopal effect by design. The abscopal effect is thought to arise when dead or damaged tumor cells release antigens that teach some types of immune cells to recognize and attack other and even distant cancer cells. Essentially, the treated tumor behaves like a personalized cancer vaccine that incites the immune system to attack metastasized tumors. The advent of cancer immunoadjuvants, which enhance and sustain the activity of tumor-targeting immune cells, has been a key to unlocking the abscopal effect, at least in the laboratory setting. 

In the clinic, success has proven more elusive. Since immunotherapies can lead to serious toxicities if administered through the bloodstream, they must be delivered directly to the tumor — often by injection. It is difficult for clinicians to target injections precisely to the tumor and impossible to confirm delivery. Once injected, immunostimulatory drugs quickly leak out of the tumor before they have had a chance to take full effect.

MIT researchers, together with colleagues from Mass General Brigham, have developed a polymer gel delivery system that could help translate the promise of the abscopal effect into the clinic. The gel, visible with a CT scanner or ultrasound, solidifies after injection, where it remains in the tumor to release drugs at a controlled rate.

In a study published in Advanced Healthcare Materials, the team delivered the immune-stimulating drug imiquimod in combination with checkpoint blockade therapy to dual-tumor mouse models of colon and breast cancer, which showed improved survival as well as tumor regression in both treated and untreated tumors.

“The field has been seeking the ‘holy grail’ of the abscopal effect for the past 15 years,” says Giovanni Traverso, a senior author of the study, Karl Van Tassel Career Development Professor in the Department of Mechanical Engineering, and a member of the Koch Institute for Integrative Cancer Research at MIT. “Now, with drug-delivery materials better adapted for the clinic, it could be within reach.”

Traverso’s co-senior author is Umar Mahmood, director of the Center for Precision Imaging and chief of the Division of Nuclear Medicine and Molecular Imaging at Massachusetts General Hospital (MGH). Avik Som, interventional and diagnostic radiology resident at MGH; Jan-Georg Rosenboom, senior postdoc in the Langer and Traverso labs at the Koch Institute; and  Eric Wehrenberg-Klee, director of the Center for Image-Guided Cancer Therapy and assistant professor at Harvard Medical School, are co-lead authors. Robert Langer, David H. Koch Institute Professor, is also an author of the study.

Defining the problem

At MGH, clinicians saw that of 18 patients that were treated with an intratumoral injection of immunotherapy either just before or after undergoing a procedure known as cryoablation, one patient with metastatic melanoma showed a sustained abscopal effect. In cryoablation, a tumor is injected with freezing gas and then thawed out, with the hope of inducing a system-wide immune response to tumors.

The observation pointed to a promising avenue for achieving the abscopal effect for more patients, but a new tool was needed to address some of the realities of intratumoral injections in the clinic. In addition to the difficulties of delivering intratumoral injections for the clinician, these treatments are costly and infeasible for patients. Because tumors do not retain immunotherapies for long, patients require repeat injections — with sedation — over several days. The clinicians looked across the river to their MIT colleagues for help.

 “My clinical colleagues came to us with this very interesting problem, so we thought, how can we address this from our own chemical engineering perspective?” says Rosenboom.

The interdisciplinary team determined that the injected material would need to be liquid at room temperature during injection, and then solidify once inside the tumor to prevent leakage. For optimal drug delivery, the gel would need to carry a high concentration of drug in a small volume and then release its payload in a controlled fashion over several days. The team planned to add an iodinated and clinically approved contrast agent to make it visible with a CT scan to help clinicians confirm they have successfully injected the material. To help smooth the path of the platform to the clinic, the gel should be known to be safe and biocompatible and the immunotherapy it transports to have proven effectiveness.

“As a radiologist, I can see tumors under CT or ultrasound, but I can't see the drugs they are asking me to inject!” says Som. “That's why we designed a formulation for a promising immunoadjuvant that could be image guided by both modalities. This platform should hopefully realize the immense promise of personalized cancer vaccines.”

Adds Wehrenberg-Klee, “When developing new intratumoral immunotherapies, being able to confirm delivery into tumor is a critical variable. Intratumoral immunotherapy relies on the assumption that you are delivering therapy to tumor, but our clinical experience suggests this may not always be true. If we can see what we’ve injected, we can eliminate that concern.”

“As engineers, we needed to solve the problem of how to tune a polymer formulation to achieve injectability, solidification at body temperature, prolonged drug release, and visibility — all at the same time, all while these properties affect one another,” says Rosenboom. “That took us about four years to figure out.”

A solution gels

After investigating several polymers, the researchers found that a three-part polymer called PLGA-PEG-PLGA would help them balance the several competing features required of their platform. The polymer is thermosensitive. With slight changes to its molecular weight (size), it can be adjusted to be liquid at room temperature during injection and more viscous in the warmer environment of the tumor.

The polymer is also amphiphilic, with a PEG block that is attracted to water and two PLGA blocks that repel water, so that it forms a nanoparticle around the hydrophobic drug. Its amphiphilic properties allow its drug-release behaviors to be precisely tuned: the more hydrophobic the PLGA block, the slower the release. The formulation allowed a slowed drug release over four to five days, which was a timeframe previously reported to be effective when injected daily.

A similar version of the polymer has already been studied in clinical trials for delivering a type of chemotherapy, paclitaxel. However, in this scenario, the gel would transport imiquimod, an immunotherapy already approved by the Food and Drug Administration (FDA) that is commonly used topically to treat basal cell carcinoma.

Once the gel had been tailored to meet their requirements, the team tested it in mouse models of colon and breast cancer that are usually resistant to immunotherapy. In combination with a type of immunotherapy called checkpoint blockade therapy, they used the platform to deliver imiquimod. Each mouse had two tumors of the same type, but only one tumor was treated. If both tumors regressed, then the researchers could confirm their platform could induce a system-wide immune response to tumors — the abscopal effect.

Overall, the combination of checkpoint blockade therapy and intratumorally delivered imiquimod resulted in improved survival in both colon and breast cancer models. The treatment resulted in an all-or-nothing response, with complete regression of both the treated and untreated tumors in the mice that did respond to therapy. For nonresponders, there was no regression in either tumor. The researchers also tested the combination therapy of gel-delivered imiquimod and checkpoint blockade therapy with and without cryoablation of the treated tumor and found that the two approaches gave similar results.

Because the platform is made from safe materials to deliver an already-approved drug, the team expects that the path to FDA approval will be significantly shorter than for completely novel platforms and therapies. The team is also working with industry partners to adapt the platform for treating other tumor types and to deliver other therapies.

This study was funded in part by a Philips RSNA Research Award, a Schlaeger Research Fellowship, a postdoctoral fellowship from the Ludwig Center at the Koch Institute, and grants from Boston Scientific, the MIT Deshpande Center for Technological Innovation, and the National Cancer Institute.

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With a quantum “squeeze,” clocks could keep even more precise time, MIT researchers propose

The practice of keeping time hinges on stable oscillations. In a grandfather clock, the length of a second is marked by a single swing of the pendulum. In a digital watch, the vibrations of a quartz crystal mark much smaller fractions of time. And in atomic clocks, the world’s state-of-the-art timekeepers, the oscillations of a laser beam stimulate atoms to vibrate at 9.2 billion times per second. These smallest, most stable divisions of time set the timing for today’s satellite communications, GPS systems, and financial markets.

A clock’s stability depends on the noise in its environment. A slight wind can throw a pendulum’s swing out of sync. And heat can disrupt the oscillations of atoms in an atomic clock. Eliminating such environmental effects can improve a clock’s precision. But only by so much.

A new MIT study finds that even if all noise from the outside world is eliminated, the stability of clocks, laser beams, and other oscillators would still be vulnerable to quantum mechanical effects. The precision of oscillators would ultimately be limited by quantum noise.

But in theory, there’s a way to push past this quantum limit. In their study, the researchers also show that by manipulating, or “squeezing,” the states that contribute to quantum noise, the stability of an oscillator could be improved, even past its quantum limit.

“What we’ve shown is, there’s actually a limit to how stable oscillators like lasers and clocks can be, that’s set not just by their environment, but by the fact that quantum mechanics forces them to shake around a little bit,” says Vivishek Sudhir, assistant professor of mechanical engineering at MIT. “Then, we’ve shown that there are ways you can even get around this quantum mechanical shaking. But you have to be more clever than just isolating the thing from its environment. You have to play with the quantum states themselves.”

The team is working on an experimental test of their theory. If they can demonstrate that they can manipulate the quantum states in an oscillating system, the researchers envision that clocks, lasers, and other oscillators could be tuned to super-quantum precision. These systems could then be used to track infinitesimally small differences in time, such as the fluctuations of a single qubit in a quantum computer or the presence of a dark matter particle flitting between detectors.

“We plan to demonstrate several instances of lasers with quantum-enhanced timekeeping ability over the next several years,” says Hudson Loughlin, a graduate student in MIT’s Department of Physics. “We hope that our recent theoretical developments and upcoming experiments will advance our fundamental ability to keep time accurately, and enable new revolutionary technologies.”

Loughlin and Sudhir detail their work in an open-access paper published in the journal Nature Communications.

Laser precision

In studying the stability of oscillators, the researchers looked first to the laser — an optical oscillator that produces a wave-like beam of highly synchronized photons. The invention of the laser is largely credited to physicists Arthur Schawlow and Charles Townes, who coined the name from its descriptive acronym: light amplification by stimulated emission of radiation.

A laser’s design centers on a “lasing medium” — a collection of atoms, usually embedded in glass or crystals. In the earliest lasers, a flash tube surrounding the lasing medium would stimulate electrons in the atoms to jump up in energy. When the electrons relax back to lower energy, they give off some radiation in the form of a photon. Two mirrors, on either end of the lasing medium, reflect the emitted photon back into the atoms to stimulate more electrons, and produce more photons. One mirror, together with the lasing medium, acts as an “amplifier” to boost the production of photons, while the second mirror is partially transmissive and acts as a “coupler” to extract some photons out as a concentrated beam of laser light.

Since the invention of the laser, Schawlow and Townes put forth a hypothesis that a laser’s stability should be limited by quantum noise. Others have since tested their hypothesis by modeling the microscopic features of a laser. Through very specific calculations, they showed that indeed, imperceptible, quantum interactions among the laser’s photons and atoms could limit the stability of their oscillations.

“But this work had to do with extremely detailed, delicate calculations, such that the limit was understood, but only for a specific kind of laser,” Sudhir notes. “We wanted to enormously simplify this, to understand lasers and a wide range of oscillators."

Putting the “squeeze” on

Rather than focus on a laser’s physical intricacies, the team looked to simplify the problem.

“When an electrical engineer thinks of making an oscillator, they take an amplifier, and they feed the output of the amplifier into its own input,” Sudhir explains. “It’s like a snake eating its own tail. It’s an extremely liberating way of thinking. You don’t need to know the nitty gritty of a laser. Instead, you have an abstract picture, not just of a laser, but of all oscillators.”

In their study, the team drew up a simplified representation of a laser-like oscillator. Their model consists of an amplifier (such as a laser’s atoms), a delay line (for instance, the time it takes light to travel between a laser’s mirrors), and a coupler (such as a partially reflective mirror).

The team then wrote down the equations of physics that describe the system’s behavior, and carried out calculations to see where in the system quantum noise would arise.

“By abstracting this problem to a simple oscillator, we can pinpoint where quantum fluctuations come into the system, and they come in in two places: the amplifier and the coupler that allows us to get a signal out of the oscillator,” Loughlin says. “If we know those two things, we know what the quantum limit on that oscillator’s stability is.”

Sudhir says scientists can use the equations they lay out in their study to calculate the quantum limit in their own oscillators.

What’s more, the team showed that this quantum limit might be overcome, if quantum noise in one of the two sources could be “squeezed.” Quantum squeezing is the idea of minimizing quantum fluctuations in one aspect of a system at the expense of proportionally increasing fluctuations in another aspect. The effect is similar to squeezing air from one part of a balloon into another.

In the case of a laser, the team found that if quantum fluctuations in the coupler were squeezed, it could improve the precision, or the timing of oscillations, in the outgoing laser beam, even as noise in the laser’s power would increase as a result.

“When you find some quantum mechanical limit, there’s always some question of how malleable is that limit?” Sudhir says. “Is it really a hard stop, or is there still some juice you can extract by manipulating some quantum mechanics? In this case, we find that there is, which is a result that is applicable to a huge class of oscillators.”

This research is supported, in part, by the National Science Foundation.

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Q&A: Phillip Sharp and Amy Brand on the future of open-access publishing

Providing open access to scholarly publications is a long-running issue with new developments on the horizon. Last year, the U.S. federal government’s Office of Science and Technology Policy mandated that starting in 2026 publishers must provide open access to publications stemming from federal funding. That provides more impetus for the open-access movement in academia.

Meanwhile, other trends are changing academic publishing, including consolidation of journal titles and provision of access by having authors (and their home institutions) pay for publication costs. With these developments unfolding, a group of MIT scholars is releasing a new white paper about academic open-access publishing. The paper gathers information, identifies outstanding questions, and calls for further research and data to inform policy on the subject.

The group was chaired by Institute Professor Emeritus Phillip A. Sharp, of the Department of Biology and Koch Institute of Integrative Cancer Research, who co-authored the report along with William B. Bonvillian, senior director of special projects at MIT Open Learning; Robert Desimone, director of the McGovern Institute for Brain Research; Barbara Imperiali, the Class of 1922 Professor of Biology; David R. Karger, professor of electrical engineering; Clapperton Chakanetsa Mavhunga, professor of science, technology, and society; Amy Brand, director and publisher of the MIT Press; Nick Lindsay, director for journals and open access at MIT Press; and Michael Stebbins of Science Advisors, LLC.

MIT News spoke with Sharp and Brand about the state of open-access publishing.

Q: What are the key benefits of open access, as you see it?

Amy Brand: As an academic publisher running the MIT Press, we have embraced open access in both books and journals for a long time because it is our mission to support our authors and get their research out into the world. Whether it’s completely removing paywalls and barriers, or keeping prices low, we do whatever we can to disseminate the content that we publish. Even before we were talking about federal policies, this was a priority at the MIT Press.

Phillip Sharp: As a scientist, I’m interested in having my research make the largest impact it can, to help solve some of the challenges of society. And open access, making research available to people around the world, is an important aspect of that. But the quality of research is dependent upon peer review. So, I think open access policies need to be considered and promoted in the context of a very valuable and vigorous peer-review publication process.

Q: What are the key elements of this report?

Brand: The first part of the report is a history of open access, and the second part is a list of questions driving toward evidence-based policy. On the one hand, there are questions such as: How does policy impact the day-to-day work of researchers and their students? What are the impacts on the lab? Other questions have to do with the impacts on the publishing industry. One reason I was invested in doing this is concerns about the impact on nonprofit publishers, on university presses, on scientific societies that publish. Some of the questions we raise have to do with understanding the impact on smaller, nonprofit publishers and ultimately knowing how to protect their viability.

Sharp: The current policies for open access being required by OSTP’s Nelson Memo dramatically change who is paying for publication, where the resources come from for publication. It puts a lot of emphasis on the research institute or other sources to cover that. And that raises another issue in open access: Will this limit publications from researchers at institutes that cannot afford the charge? The scientific community is very international, and the impact of science in many countries is incredibly important. So dealing with the [impact of] open access is something that needs to be developed with evidence and policy.

The report notes that if open access was covered by an institution for all publications at $3,000 per article, MIT’s total cost would be $25 million per year. That’s going to be a challenge. And if it’s a challenge for MIT, it’s going to be an enormous challenge in a number of other places.

Q: What are some additional points about open access that we should keep in mind?

Brand: The Nelson Memo also provides that self-archiving is one of the ways to comply with the policy — which means authors can take an earlier version of an article and put it in an institutional repository. Here at MIT we have the DSpace repository that contains many of the papers that faculty publish. The economics of that are very different, and it’s also a little unclear how that’s going to play out. We recently saw one scientific society decide to implement a charge around that, something the community has never seen before.

But as we essentially have a system that already creates incentives for publishers to increase these article processing charges, the publication charges, there are a lot of questions about how publishers who do high-quality peer review will be sustained, and where that money is going to come from.

Sharp: When you come to the data side of the issue, it’s complicated because of the value of the data itself. It’s important that data is collected and has metadata about the research process that’s been made available to others. It’s also time to talk about this in the academic community.

Q: The report makes clear that there are multiple trends here: consolidation in for-profit publishing, growth of open-access publications, fiscal pressure on university libraries, and now the federal mandate. Complicated as the present may be, it does seem that MIT wants to look ahead on this issue.

Brand: I do think in the publishing community, and certainly in the university press community, we’ve been way out in front on this for a while, and with some of the business models we helped implement and test and create, we’re finding other publishers are following suit and they are interested. But right now, with the new federal policy, most publishers have no choice but to begin asking: What does sustainable high-quality publishing mean if, as a publisher, I have to distribute all or some of this content in open digital form?

Sharp: The purpose of this report is to stimulate that conversation: more numbers, every bit of evidence. Communities have been responsible for the quality of science in different disciplines, and sharing the repsonsbility of peer review is something that motivates a lot of engagement. Sustaining that is important for the discipline. Without that sustainability, there will be slower progress in science, in my opinion.

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Pushing the frontiers of art and technology with generative AI

Many people are scrambling to predict how AI will impact society. But living in a world of ubiquitous computing has already changed us in ways we might not fully appreciate. Generative AI-aided art — like all art — can be a powerful tool to visualize those changes, broaden our perceptions, and inspire us all.

That was the message of a keynote talk by artist Refik Anadol on the first day of MIT’s Generative AI Week. Anadol walked the audience through his studio’s body of work, which includes public art displays and other digital creations that visualize human and machine intelligence around the world.

“I’m inspired by the idea of how our perceptions of physical and virtual worlds are transforming us,” Anadol explained to a packed Kresge Auditorium.

The presentation was part of a full day of events that also included panels on generative AI’s potential applications and impact on society, with opening presentations from iRobot founder Rodney Brooks and MIT President Sally Kornbluth. The goal of the week of events is to bring together MIT’s community to spotlight insights from MIT’s researchers, stimulate thoughtful analysis, and engage in critical dialogues on the implications and possibilities of generative AI. Other days feature symposia on generative AI and education, creativity, and commerce.

Anadol’s work uses generative AI-based aesthetics on top of data from things like real-time weather data, changing climates and landscapes, historic architecture, and more. Some of his projects even incorporate AI-generated smells. A growing portion of Anadol’s work uses generative AI to visualize data and the physical world in new ways and change people’s perspectives of their surroundings and themselves. Part of that work leverages hallucinations — or creations by machines that are often a source of frustration for computer scientists.

“It’s really inspiring to see how we can reconstruct this information through AI’s hallucinations to compose a new form of art-making and space-making,” Anadol said.

For one of Anadol’s projects, he combined a dataset of approximately 100 million images of coral reefs with generative AI and visual art techniques to show vibrant, morphing coral images based on actual corals found in nature. The project sought to raise awareness of climate change by emphasizing the importance of coral preservation.

Another project Anadol discussed used real-time climate data in Barcelona to generate an array of digital patterns that were projected onto the famous Casa Batlló created by renowned architect Antoni Gaudí. The display was later sold as a nonfungible digital token, or NFT, with a portion of proceeds donated to institutions that work with neurodiverse adults and children.

“I believe light, data, and AI, when connected, can create a new form of architecture, which I call sensing architecture,” Anadol explained.

A third project was sparked by Anadol’s experience watching his uncle struggle with Alzheimer’s disease. The experience led the artist to consider new ways of visualizing neurological data in a way that provokes fundamental questions about the human brain and mental health. Anadol later received permission from patients to use their datasets, collected by electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI), to create a multisensory, immersive art exhibit and to promote mental health through art.

“Our fundamental goal is to find dreams of reality and concepts of reality,” Anadol said. “It’s about trying to find new ways of speculating, and I think the future of imagination, with neural networks and the integration of materials, [offers] a lot of room for creatives to recombine and explore connections between humanity.”

Through each of the projects, Anadol seeks to enhance our ability to express ourselves and find meaning.

“I believe by using AI, whether generative or otherwise, we have the opportunity to find the language of humanity,” Anadol said.

Speaking in front of a large screen displaying each of the projects, Anadol’s presentation gave the audience vivid examples of how generative AI technology is changing the world of art. Speaking in roundtable discussions after the talk, MIT professors gave more examples of how the technology could transform other fields, from transportation and manufacturing to health care, finance, and music.

One of those presenters was Cathy Wu, an assistant professor in the Department of Civil and Environmental Engineering. Wu described how generative AI could be used to create synthetic data to help prepare self-driving cars for rare events, better model traffic patterns, and improve zoning regulations to ease housing shortages.

In conducting her research, Wu said she was surprised to find so many promising applications for generative AI, and said she’s cautiously optimistic it will contribute to some of the transportation industry’s hardest problems.

“Longstanding issues are longstanding issues, and generative AI by itself will not move the needle, but it adds one very powerful tool to the toolbox,” Wu said. “I’m very encouraged that for some of these challenges, generative AI might just give us the push we need to make an impact.”

Another speaker was Marzyeh Ghassemi, an assistant professor in the Department of Electrical Engineering and Computer Science. Ghassemi showed how some models can perpetuate unequal outcomes by recommending African Americans exhibiting violent behavior be sent to jail while recommending their white counterparts be sent to a hospital.

Still, Ghassemi showed that the way decision makers interact with models ultimately determines if they exacerbate biases.

“Maybe we can get to safe integration [of these tools] without perfect models, as some other industries like aviation have done,” Ghassemi said. “If we want to move forward with AI in health care, we need to recognize that this is an ongoing process and it’s going to require diverse data and [consideration of diverse] needs.”

All of the examples presented in the afternoon described a technology whose ultimate effect on society should be determined by the people it impacts most.

“The impact of bringing generative AI to different fields is captivating,” Anadol said toward the end of his presentation. “By co-creating with musicians, other artists, and the public, there’s a beautiful, positive future to explore.”

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Five high schoolers awarded MIT OMEGA scholarships for intergenerational efforts

The MIT AgeLab awards annual scholarships to high school students who lead or develop intergenerational programs — initiatives designed to bring together younger and older people — in their communities. On Sept. 29, five $5,000 OMEGA scholarships were given to high school students across the United States, with support from AARP Massachusetts. An additional $1,000 was awarded to each winning intergenerational program to help sustain and grow the students’ efforts.

OMEGA, which stands for Opportunities for Multigenerational Exchange, Growth, and Action, develops programming and offers scholarships to facilitate intergenerational connections between younger people and older adults in their communities.

The scholarships were awarded at a virtual ceremony hosted by the MIT AgeLab, with representatives from the AgeLab and AARP in attendance, along with the scholarship winners, their parents, program participants, and community partners.

“OMEGA is a reminder to all of us that there are new generations committed to intergenerational solutions, not only for the challenges of aging, but also for unlocking the opportunities of living longer,” says Michael E. Festa, state director of AARP Massachusetts.

Intergenerational programs help to strengthen social ties within communities and facilitate knowledge transfer between younger and older adults. Two of the winning programs for 2023, a book club focused on discussing feminist literature and a project uncovering the history of a historically Black neighborhood, focus on bringing together and centering the voices of historically marginalized communities.

The five scholarship winners and their winning programs are:

Hannah Paseltiner, currently a first-year student at the State University of New York at Binghamton, and a 2023 graduate of Clarkstown High School in New City, New York. Paseltiner founded the Elderly Allies Club, which works to build relationships between younger adults and communities of older people, including nursing homes and assisted living communities, in New City. The program partners with the Rockland County Village Community, a social and mutual support community for older adults. Members of the club make personal deliveries on behalf of nursing home residents, craft décor for assisted living communities, and organize “speed-dating” and storytelling events between younger and older adults.

Sarah Adams, currently a senior at East High School in Rochester, New York. Adams is a Youth History Ambassador for Clarissa Uprooted, a collaboration between the Center for Teen Empowerment and the Clarissa Street Reunion Committee. The project aims to preserve and transmit knowledge about the history of the Clarissa Street “village” in Rochester, New York, a historically Black neighborhood that was gutted by urban renewal policies in the 1950s and ’60s. Relying on the historical memory of older adults in the community, the initiative produced a documentary titled Clarissa Uprooted, and is developing a school curriculum to teach the history of the neighborhood to students in Monroe County.

India Ratha, currently a first-year student at Carleton College in Minnesota, and a 2023 graduate of Tech High School in St. Cloud, Minnesota. Ratha joined and later became an organizer of an initiative called Sounds of Sunday, which brings high school musicians into nursing homes for musical performances and intergenerational conversations. Sounds of Sunday has partnered with the Central Minnesota Council on Aging, as well as the Coalition to End Social Isolation and Loneliness for Central Minnesota.

Lorenzo Martinelli, currently a first-year student at the University of Chicago, and a 2023 graduate of Saint Xavier High School in Louisville, Kentucky. Martinelli is a co-founder of a program called Tandem, based in Louisville. Founded during the Covid-19 pandemic, when social isolation was a major challenge for people of all ages, Tandem facilitates ongoing friendships between older adults and high school students through 30-minute phone conversations. Over two-and-a-half years, the program has facilitated over 900 calls and 450 hours of deep conversation between pairs of older and younger adults.

Vienna Rivard, currently a first-year student at the University of Massachusetts at Amherst, and a 2023 graduate of Hopkinton High School in Massachusetts. Rivard founded an intergenerational feminist book club in her community in Hopkinton, connecting students with members of the Hopkinton’s Women’s Club. The group gathers students and older adults to engage in discussion about their readings, attend field trips to local historical museums, and share their past and present experiences as women. The group originally met over Zoom, before moving to community settings including the outdoors and local libraries.

The AgeLab’s OMEGA program works in a variety of ways with students to develop their intergenerational programs. The MIT AgeLab was created in 1999 within the MIT Center for Transportation and Logistics to invent new ideas and creatively translate technologies into practical solutions that improve people's health and enable them to “do things” throughout their lifespan. Equal to the need for ideas and new technologies for older adults is the belief that innovations in how products are designed, services are delivered, or policies are implemented are of critical importance to our quality of life tomorrow.

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Elly Nedivi receives 2023 Kreig Cortical Kudos Discoverer Award

The Cajal Club has named Elly Nedivi, William R. and Linda R. Young Professor of Neuroscience in The Picower Institute for Learning and Memory, the 2023 recipient of the Krieg Cortical Kudos Discoverer Award.

The club’s award, first bestowed in 1987, honors outstanding established investigators studying the cerebral cortex, the brain’s outer layers where circuits of neurons enable functions ranging from sensory processing to cognition. These circuits can constantly remodel their connections to adapt the brain to experience, a phenomenon called plasticity, that underlies learning and memory.

With a focus on the visual cortex, Nedivi’s lab investigates the molecular and cellular mechanisms that enable plasticity in the developing and adult brain, including identification of the genes whose expression is involved, characterization of the cellular functions of the proteins those genes encode, and studies of synaptic and neuronal remodeling as it happens in live, behaving animals. To enable those observations, Nedivi and longtime collaborator Peter So, professor of mechanical engineering, have developed advanced microscopy systems that can image multiple components of neural connections in the cortex of live rodents.

In a message to Nedivi notifying her of the honor, Cajal Club president Leah Kurbitzer, professor of psychology at the University of California at Davis, said: “This award recognizes your outstanding and continuous contributions to our understanding of fundamental aspects of cortical connectivity in the mammalian brain, and the cellular and molecular mechanisms underlying adult visual experience plasticity. Your work examining both the effects of visual experience manipulations and the functions of activity-induced candidate plasticity genes, by using advanced state-of-the-art in vivo multiphoton imaging technologies and sophisticated molecular genetic manipulations to expose fundamental mechanisms of brain plasticity, has made you a leader in the field, and an exceptional Krieg Cortical Discoverer award winner.”

Nedivi said she was honored to receive the award. The club conferred it Nov. 12 at its annual social during the Society for Neuroscience Annual Meeting in Washington.

“I am honored to be recognized with this award and to be following in the footsteps of many previous recipients whose work I admire and respect,” says Nedivi, a faculty member of MIT’s departments of Biology and of Brain and Cognitive Sciences.

Previous honorees with Picower Institute ties include Newton Professor of Neuroscience Mriganka Sur and Picower Institute Scientific Advisory Board member Carla Shatz, a professor at Stanford University. Nedivi’s former trainee Jerry Chen, now an associate professor at Boston University, and Sur’s former trainee Anna Majewska, now a professor at the University of Rochester, have each won Krieg Cortical Explorer awards, which are given to researchers at an earlier career stage.

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A new way to see the activity inside a living cell

Living cells are bombarded with many kinds of incoming molecular signal that influence their behavior. Being able to measure those signals and how cells respond to them through downstream molecular signaling networks could help scientists learn much more about how cells work, including what happens as they age or become diseased.

Right now, this kind of comprehensive study is not possible because current techniques for imaging cells are limited to just a handful of different molecule types within a cell at one time. However, MIT researchers have developed an alternative method that allows them to observe up to seven different molecules at a time, and potentially even more than that.

“There are many examples in biology where an event triggers a long downstream cascade of events, which then causes a specific cellular function,” says Edward Boyden, the Y. Eva Tan Professor in Neurotechnology. “How does that occur? It’s arguably one of the fundamental problems of biology, and so we wondered, could you simply watch it happen?”

The new approach makes use of green or red fluorescent molecules that flicker on and off at different rates. By imaging a cell over several seconds, minutes, or hours, and then extracting each of the fluorescent signals using a computational algorithm, the amount of each target protein can be tracked as it changes over time.

Boyden, who is also a professor of biological engineering and of brain and cognitive sciences at MIT, a Howard Hughes Medical Institute investigator, and a member of MIT’s McGovern Institute for Brain Research and Koch Institute for Integrative Cancer Research, as well as the co-director of the K. Lisa Yang Center for Bionics, is the senior author of the study, which appears today in Cell. MIT postdoc Yong Qian is the lead author of the paper.

Fluorescent signals

Labeling molecules inside cells with fluorescent proteins has allowed researchers to learn a great deal about the functions of many cellular molecules. This type of study is often done with green fluorescent protein (GFP), which was first deployed for imaging in the 1990s. Since then, several fluorescent proteins that glow in other colors have been developed for experimental use.

However, a typical light microscope can only distinguish two or three of these colors, allowing researchers only a tiny glimpse of the overall activity that is happening inside a cell. If they could track a greater number of labeled molecules, researchers could measure a brain cell’s response to different neurotransmitters during learning, for example, or investigate the signals that prompt a cancer cell to metastasize.

“Ideally, you would be able to watch the signals in a cell as they fluctuate in real time, and then you could understand how they relate to each other. That would tell you how the cell computes,” Boyden says. “The problem is that you can’t watch very many things at the same time.”

In 2020, Boyden’s lab developed a way to simultaneously image up to five different molecules within a cell, by targeting glowing reporters to distinct locations inside the cell. This approach, known as “spatial multiplexing,” allows researchers to distinguish signals for different molecules even though they may all be fluorescing the same color.

In the new study, the researchers took a different approach: Instead of distinguishing signals based on their physical location, they created fluorescent signals that vary over time. The technique relies on “switchable fluorophores” — fluorescent proteins that turn on and off at a specific rate. For this study, Boyden and his group members identified four green switchable fluorophores, and then engineered two more, all of which turn on and off at different rates. They also identified two red fluorescent proteins that switch at different rates, and engineered one additional red fluorophore.

Each of these switchable fluorophores can be used to label a different type of molecule within a living cell, such an enzyme, signaling protein, or part of the cell cytoskeleton. After imaging the cell for several minutes, hours, or even days, the researchers use a computational algorithm to pick out the specific signal from each fluorophore, analogous to how the human ear can pick out different frequencies of sound.

“In a symphony orchestra, you have high-pitched instruments, like the flute, and low-pitched instruments, like a tuba. And in the middle are instruments like the trumpet. They all have different sounds, and our ear sorts them out,” Boyden says.

The mathematical technique that the researchers used to analyze the fluorophore signals is known as linear unmixing. This method can extract different fluorophore signals, similar to how the human ear uses a mathematical model known as a Fourier transform to extract different pitches from a piece of music.

Once this analysis is complete, the researchers can see when and where each of the fluorescently labeled molecules were found in the cell during the entire imaging period. The imaging itself can be done with a simple light microscope, with no specialized equipment required.

Biological phenomena

In this study, the researchers demonstrated their approach by labeling six different molecules involved in the cell division cycle, in mammalian cells. This allowed them to identify patterns in how the levels of enzymes called cyclin-dependent kinases change as a cell progresses through the cell cycle.

The researchers also showed that they could label other types of kinases, which are involved in nearly every aspect of cell signaling, as well as cell structures and organelles such as the cytoskeleton and mitochondria. In addition to their experiments using mammalian cells grown in a lab dish, the researchers showed that this technique could work in the brains of zebrafish larvae.

This method could be useful for observing how cells respond to any kind of input, such as nutrients, immune system factors, hormones, or neurotransmitters, according to the researchers. It could also be used to study how cells respond to changes in gene expression or genetic mutations. All of these factors play important roles in biological phenomena such as growth, aging, cancer, neurodegeneration, and memory formation.

“You could consider all of these phenomena to represent a general class of biological problem, where some short-term event — like eating a nutrient, learning something, or getting an infection — generates a long-term change,” Boyden says.

In addition to pursuing those types of studies, Boyden’s lab is also working on expanding the repertoire of switchable fluorophores so that they can study even more signals within a cell. They also hope to adapt the system so that it could be used in mouse models.

The research was funded by an Alana Fellowship, K. Lisa Yang, John Doerr, Jed McCaleb, James Fickel, Ashar Aziz, the K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics at MIT, the Howard Hughes Medical Institute, and the National Institutes of Health.

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MIT’s Science Policy Initiative holds 13th annual Executive Visit Days

From Oct. 23-24, a delegation consisting of 21 MIT students, one MIT postdoc, and four students from the University of the District of Columbia met in Washington for the MIT Science Policy Initiative’s Executive Visit Days (ExVD). Now in its 13th cycle, this trip offers a platform where university students and young researchers can connect with officials and scientists from different federal agencies, discuss issues related to science and technology policy, and learn about the role the federal government plays in addressing these issues.

The delegation visited seven different agencies, as well as the MIT Washington Office, where the group held virtual calls with personnel from the National Institutes of Health and the Advanced Research Projects Agency for Health. Visits to the National Science Foundation, Department of Energy Office of Science, White House Office of Science and Technology Policy (OSTP), Environmental Protection Agency, and National Aeronautics and Space Administration then followed over the course of two days. The series of meetings, facilitated by the MIT Science Policy Initiative (SPI), offered a window into the current activities of each agency and how individuals can engage with science policy through the lens of each particular agency.

The Science Policy Initiative is an organization of students and postdocs whose core goal is not only to grow interest at MIT and in the community at large in science policy, but also to facilitate the exchange of ideas between the policymakers of today and the scientists of tomorrow. One of the various trips organized by SPI every year, ExVD allows students to gain insight into the work of federal agencies, while also offering the chance to meet with representatives from these agencies, many of whom are MIT alumni, and discuss their paths toward careers in science policy. Additionally, ExVD serves as an opportunity for participants to network with students, postdocs, and professionals outside of their fields but united by common interests in science policy. 

“I believe it is critical for students with vital technical expertise to gain a sense of the realities of policymaking,” says Phillip Christoffersen, a PhD student researching AI in MIT’s Department of Electrical Engineering and Computer Science and SPI ExVD 2023 chair. “Due to the many complexities of modern life, we are simultaneously reaching tipping points in many fields — AI, climate change, biotechnology, among many others. For this reason, science and science policy must increasingly move in lockstep for the good of society, and it falls on us as scientists-in-training to make that happen.”

One example of the delegation’s visits was to the White House OSTP, located directly next to the West Wing at the Eisenhower Executive Office Building. This special agency of fewer than 200 staff, most of whom are either in rotation or on loan from other federal agencies, directly reports to the president on all matters related to science and policy. The atmosphere at the White House complex and the exchanges with Kei Koizumi, principal deputy director for policy at OSTP, deeply inspired the students and showcased the vast impact science can have on federal policy.

The overall sentiment among the ExVD participants has been that of reborn motivation, having become inspired to participate in policy matters, either as a portion of their graduate research or in their future career. The ExVD 2023 cohort is thankful to the MIT Washington office, whose generous support was crucial to making this trip a reality. Furthermore, the delegation thanks the MIT Science Policy Initiative’s leadership team for organizing this trip, enabling an extremely meaningful experience.

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Serious play at the MIT Game Lab

Students fill the glass-walled room and spill out into the common area. They gather around tables and desks cluttered with board games and game pieces. Along the far wall, large screens show students exploring the latest virtual reality experience alongside classmates reliving their favorite retro videogames.

Welcome to an open house of the MIT Game Lab, where play and experimentation are joined by serious inquiry about the gaming industry and its role in society.

In addition to its rollicking open houses, which take place at least once a semester, the Game Lab hosts public events, organizes research projects, and teaches courses through MIT Comparative Media Studies/Writing (CMS/W).

The Game Lab’s work is designed to help students think critically about the games they’ve often been playing for years without considering the values they might project, and to prepare them to engage in thoughtful design practices themselves.

“Students come to the Game Lab because it sounds like fun, which is great, but they realize through our research that there’s also something really serious at work in games,” Game Lab Director and Professor T.L. Taylor says. “I think students often have this moment where they realize this thing they’ve been enjoying actually has a lot of stakes in it; these are things that really matter.”

The Game Lab analyzes the gaming industry and its impact, explores new technologies and formats, and creates games that tackle important issues. Many new games are tied to larger research projects.

“There’s a desire from our students to express themselves through games, whether that’s through making educational games or games with specific messages or lessons,” says Game Lab research scientist and lecturer Mikael Jakobsson. “Games are a big part of most people’s lives, so there’s a thirst among our students for not only learning how to make games, but also studying games as social and cultural artefacts.”

Through that research, students come to appreciate the impact of games on the world.

“Game are hugely important in society and culture,” Taylor says. “We’re really trying to always think critically and productively about what we do with this powerful form of media and entertainment, and to think about games as a place in which imagination and stories about the world can be worked over and thought about.”

Learning to play

The MIT Game Lab was founded in cooperation with the Singapore Ministry of Education in 2007. Early on, it would host workshops on game design with students from Singapore in the summer, then conduct teaching and research with MIT students during the school year.

The Singapore collaboration ended in 2012, but the lab continued its work, often partnering with outside companies, private donors, and other groups around campus to explore the influence of games on different aspects of society.

In one project with the Samuel Tak Lee MIT Real Estate Entrepreneurship Lab, students designed a game to explore the basics of real estate development, including managing capital and debt and deciding what sorts of buildings to build and where.

The lab also does work with communities to help them think about civic engagement. It has held workshops around the world with local students and other community members to challenge them to think about issues in their societies through the lens of game design. One such collaboration led to the game Promesa, which Jakobsson created with Puerto Rican graphic artist Rosa Colón Guerra and the design collective Popcicleta to promote what the creators call a “countercolonialist” viewpoint in the context of a game about the island’s debt crisis.

Aside from making games, researchers also consider the influence of historically popular games.

“We’re not making games as much as studying them,” says junior Michelle Liang, who works at the Game Lab as an undergraduate researcher. “It’s so easy to detach entertainment as its own separate world, when in fact media is influenced by a lot of different factors and biases. A lot of the Game Lab’s work is geared toward enhancing that understanding.”

The Game Lab’s organizers say that work distinguishes them from other gaming-focused groups in academia, which often equip students with specific skills to get jobs in the videogame industry.

“We’re not a pipeline program to go work in the gaming industry,” Taylor explains. “Some students do go into the industry, but because we’re doing critical design practice, we’re approaching games with a much broader, critically inflective perspective by thinking about things like equity and representation.”

Liang hadn’t considered the role of games in social and political issues until she discovered the Game Lab. She immediately saw the Lab as a way to combine a number of things she was passionate about.

“It’s funny to talk about my job to people,” Liang says. “Even though we are the Institute of Technology, there’s so much more MIT has to offer.”

Changing the rules

Jakobsson says the perception of games as nothing more than entertainment has led to a lack of introspection.

“The gaming industry has been a bit of a boys club where a lot of social responsibility has been shirked because they say they’re just trying to have fun and don’t have to think about how it affects society,” Jakobsson says. “Now we’re dealing with a lot of the consequences from that mindset.”

For students, involvement in the Game Lab can mean conducting research, enrolling in one of its classes, or just stopping by an open house. Regardless of how they’re exposed to the lab’s work, Taylor hopes they leave with a deeper appreciation of the power of games in our society.

“Games are a hugely important media and entertainment space, but they’re also one of our most culturally relevant and politically active spaces,” Taylor says. “Media spaces are in part where we learn about the world, for good or ill, where we construct imaginaries of the world, where we think about other possibilities. Part of the mission of CMS/W in general is taking media spaces seriously, and games are an increasingly important part of that.”

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Team engineers nanoparticles using ion irradiation to advance clean energy and fuel conversion

MIT researchers and colleagues have demonstrated a way to precisely control the size, composition, and other properties of nanoparticles key to the reactions involved in a variety of clean energy and environmental technologies. They did so by leveraging ion irradiation, a technique in which beams of charged particles bombard a material.

They went on to show that nanoparticles created this way have superior performance over their conventionally made counterparts.

“The materials we have worked on could advance several technologies, from fuel cells to generate CO₂-free electricity to the production of clean hydrogen feedstocks for the chemical industry [through electrolysis cells],” says Bilge Yildiz, leader of the work and a professor in MIT’s departments of Nuclear Science and Engineering and Materials Science and Engineering.

Critical catalyst

Fuel and electrolysis cells both involve electrochemical reactions through three principal parts: two electrodes (a cathode and anode) separated by an electrolyte. The difference between the two cells is that the reactions involved run in reverse.

The electrodes are coated with catalysts, or materials that make the reactions involved go faster. But a critical catalyst made of metal-oxide materials has been limited by challenges including low durability. “The metal catalyst particles coarsen at high temperatures, and you lose surface area and activity as a result,” says Yildiz, who is also affiliated with the Materials Research Laboratory and is an author of an open-access paper on the work published in the journal Energy & Environmental Science.

Enter metal exsolution, which involves precipitating metal nanoparticles out of a host oxide onto the surface of the electrode. The particles embed themselves into the electrode, “and that anchoring makes them more stable,” says Yildiz. As a result, exsolution has “led to remarkable progress in clean energy conversion and energy-efficient computing devices,” the researchers write in their paper.

However, controlling the precise properties of the resulting nanoparticles has been difficult. “We know that exsolution can give us stable and active nanoparticles, but the challenging part is really to control it. The novelty of this work is that we’ve found a tool — ion irradiation — that can give us that control,” says Jiayue Wang PhD ’22, first author of the paper. Wang, who conducted the work while earning his PhD in the MIT Department of Nuclear Science and Engineering, is now a postdoc at Stanford University.

Sossina Haile ’86, PhD ’92, the Walter P. Murphy Professor of Materials Science and Engineering at Northwestern University, who was not involved in the current work, says:

“Metallic nanoparticles serve as catalysts in a whole host of reactions, including the important reaction of splitting water to generate hydrogen for energy storage. In this work, Yildiz and colleagues have created an ingenious method for controlling the way that nanoparticles form.”

Haile continues, “the community has shown that exsolution results in structurally stable nanoparticles, but the process is not easy to control, so one doesn’t necessarily get the optimal number and size of particles. Using ion irradiation, this group was able to precisely control the features of the nanoparticles, resulting in excellent catalytic activity for water splitting.”

What they did

The researchers found that aiming a beam of ions at the electrode while simultaneously exsolving metal nanoparticles onto the electrode’s surface allowed them to control several properties of the resulting nanoparticles.

“Through ion-matter interactions, we have successfully engineered the size, composition, density, and location of the exsolved nanoparticles,” the team writes in Energy & Environmental Science.

For example, they could make the particles much smaller — down to 2 billionths of a meter in diameter — than those made using conventional thermal exsolution methods alone. Further, they were able to change the composition of the nanoparticles by irradiating with specific elements. They demonstrated this with a beam of nickel ions that implanted nickel into the exsolved metal nanoparticle. As a result, they demonstrated a direct and convenient way to engineer the composition of exsolved nanoparticles.

“We want to have multi-element nanoparticles, or alloys, because they usually have higher catalytic activity,” Yildiz says. “With our approach, the exsolution target does not have to be dependent on the substrate oxide itself.” Irradiation opens the door to many more compositions. “We can pretty much choose any oxide and any ion that we can irradiate with and exsolve that,” says Yildiz.

The team also found that ion irradiation forms defects in the electrode itself. And these defects provide additional nucleation sites, or places for the exsolved nanoparticles to grow from, increasing the density of the resulting nanoparticles.

Irradiation could also allow extreme spatial control over the nanoparticles. “Because you can focus the ion beam, you can imagine that you could ‘write’ with it to form specific nanostructures,” says Wang. “We did a preliminary demonstration [of that], but we believe it has potential to realize well-controlled micro- and nano-structures.”

The team also showed that the nanoparticles they created with ion irradiation had superior catalytic activity over those created by conventional thermal exsolution alone.

Additional MIT authors of the paper are Kevin B. Woller, a principal research scientist at the Plasma Science and Fusion Center (PSFC), home to the equipment used for ion irradiation; Abinash Kumar PhD ’22, who received his PhD from the Department of Materials Science and Engineering (DMSE) and is now at Oak Ridge National Laboratory; and James M. LeBeau, an associate professor in DMSE. Other authors are Zhan Zhang and Hua Zhou of Argonne National Laboratory, and Iradwikanari Waluyo and Adrian Hunt of Brookhaven National Laboratory.

This work was funded by the OxEon Corp. and MIT’s PSFC. The research also used resources supported by the U.S. Department of Energy Office of Science, MIT’s Materials Research Laboratory, and MIT.nano. The work was performed, in part, at Harvard University through a network funded by the National Science Foundation.

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A green hydrogen innovation for clean energy

Renewable energy today — mainly derived from the sun or wind — depends on batteries for storage. While costs have dropped in recent years, the pursuit of more efficient means of storing renewable power continues.

“All of these technologies, unfortunately, have a long way to go,” said Sossina Haile SB ’86, PhD ’92, the Walter P. Murphy Professor of Materials Science and Engineering at Northwestern University, at recent talk at MIT. She was the speaker of the fall 2023 Wulff Lecture, an event hosted by the Department of Materials Science and Engineering (DMSE) to ignite enthusiasm for the discipline.

To add to the renewable energy mix — and help quicken the pace to a sustainable future — Haile is working on an approach based on hydrogen in fuel cells, particularly for eco-friendly fuel in cars. Fuel cells, like batteries, produce electricity from chemical reactions but don’t lose their charge so long as fuel is supplied.

To generate power, the hydrogen must be pure — not attached to another molecule. Most methods of producing hydrogen today require burning fossil fuel, which generates planet-heating carbon emissions. Haile proposes a “green” process using renewable electricity to extract the hydrogen from steam.

When hydrogen is used in a fuel cell, “you have water as the product, and that’s the beautiful zero emissions,” Haile said, referring to the renewable energy production cycle that is set in motion.

Ammonia fuels hydrogen’s potential

Hydrogen is not yet widely used as a fuel because it’s difficult to transport. For one, it has low energy density, meaning a large volume of hydrogen gas is needed to store a large amount of energy. And storing it is challenging because hydrogen’s tiny molecules can infiltrate metal tanks or pipes, causing cracks and gas leakage.

Haile’s solution for transporting hydrogen is using ammonia to “carry” it. Ammonia is three parts hydrogen and one part nitrogen, so the hydrogen needs to be separated from the nitrogen before it can be used in the kind of fuel cells that can power cars.

Ammonia has some advantages, including using existing pipelines and a high transmission capacity, Haile said — so more power can be transmitted at any given time.

To extract the hydrogen from ammonia, Haile has built devices that look a lot like fuel cells, with cesium dihydrogen phosphate as an electrolyte. The “superprotonic” material displays high proton conductivity — it allows protons, or positively charged particles, to move through it. This is important for hydrogen, which has just a proton and an electron. By letting only protons through the electrolyte, the device strips hydrogen from the ammonia, leaving behind the nitrogen.

The material has other benefits, too, Haile said: “It’s inexpensive, nontoxic, earth-abundant — all these good things that you want to have when you think about a sustainable energy technology.”

Sparking interest — and hope

Haile’s talk piqued interest in the audience, which nearly filled the 6-120 auditorium at MIT, which seats about 150 people.

Materials science and engineering major Nikhita Law heard hope in Haile’s talk for a more sustainable future.

“A major problem in making our energy system sustainable is finding ways to store energy from renewables,” Law says. Even if hydrogen-powered cars are not as wide-scale as lithium-battery-powered electric cars, “a permanent energy storage station where we convert electricity into hydrogen and convert it back seems like it makes more sense than mining more lithium.”

Another DMSE student, senior Daniel Tong, learned about the challenges involved in transporting hydrogen at another seminar and was curious to learn more. “This was something I hadn't thought of: Can you carry hydrogen more effectively in a different form? That’s really cool.”

He adds that talks like the Wulff Lecture are helpful in keeping people up to date in a wide-ranging, interdisciplinary field such as materials science and engineering, which spans chemistry, physics, engineering, and other disciplines. “This is a really good way to get exposed to different parts of materials science. There are so many more facets than you know of.”

In her talk, Haile encouraged audience members to get involved in sustainability research.

“There’s lots of room for further insight and materials discovery,” she said.

Haile concluded by underscoring the challenges faced by developing countries in dealing with climate change impacts, particularly those near the equator where there isn’t adequate infrastructure to deal with big swings in precipitation and temperature. For the people who aren’t driven to solve problems that affect people on the other side of the world, Haile offered some extra motivation.

“I’m sure many of you enjoy coffee. This is going to put the coffee crops in jeopardy as well,” she said.

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Richard Fletcher named a 2023 Packard Fellow

The David and Lucile Packard Foundation has announced that atomic physicist Richard Fletcher, assistant professor of physics and a researcher at MIT-Harvard Center for Ultracold Atoms (CUA) and the MIT Research Laboratory of Electronics (RLE), has been named a 2023 Packard Fellow for Science and Engineering. The Packard Foundation Fellowships are one of the most prestigious and well-funded nongovernmental awards for early-career scientists.

Fletcher is one of 20 innovative early-career scientists and engineers named to the 2023 class of Packard Fellows for Science and Engineering. Two MIT alumni were also named: Ritchie Chen SM ’13, PhD ’16 and Yang Yang PhD ’16, both now at the University of California at San Francisco. Each fellow receives $875,000 over five years to pursue their research.

“It’s a tremendous honor to be awarded a Packard Fellowship, and I’m very grateful to the foundation for their support of our work,” says Fletcher. “It’s quite inspiring to look down the list of alumni, and I hope that we will live up to the same high standards.” 

Fletcher and his lab use precisely controlled gases of atoms at ultracold temperatures to create and study exciting types of quantum matter. He uses atomic vapors, which are a million times thinner than air and a million times colder than interstellar space, which in turn are manipulated by laser beams and magnetic fields, he says.

“In many systems in nature, the behavior of many particles is qualitatively different to the underlying single-particle physics,” he explains. “For example, superconductivity is the frictionless flow of electrical current, which occurs in many low-temperature materials, but you can’t understand it from the physics of a single electron. In turns out that in general, describing the emergence of macroscopic phenomena from microscopic ingredients is really hard once the rule book is quantum mechanical.

“We approach this problem by building little tailor-made quantum worlds, formed by very cold gases of atoms, a million times colder than deep space, controlled and manipulated by laser beams and magnetic fields. In particular, since these platforms are free from many of the constraints imposed by real materials, we can use them to create states of matter that nature has simply never allowed to exist before. And honestly, some of the time we just use these exquisite tools we’ve developed to simply play around and have fun in the lab, and see what surprises experiments throw our way. That’s what I love most about experimental science!”

A native of Chester, U.K., he earned his undergraduate degree in 2010 and his PhD in 2015 from Cambridge University, and in between those degrees he was a Frank Knox Fellow at Harvard University. His thesis focused on the interplay of superfluidity and Bose-Einstein condensation in two dimensions. In 2016, he arrived at MIT as a Pappalardo Fellow, working with Martin Zwierlein on quantum fluids in artificial magnetic fields, and joined the MIT faculty in 2020. In 2022 he was awarded the AFOSR Young Investigator Award.

Past Packard fellows have gone on to receive such honors as the Nobel Prize in chemistry and physics, the Fields Medal, Alan T. Waterman Awards, Breakthrough Prizes, Kavli Prizes, and elections to the national academies of Science, Engineering, and Medicine.

Each year, the foundation invites 50 universities to nominate two faculty members for consideration. The Packard Fellowships Advisory Panel, a group of 12 internationally recognized scientists and engineers, evaluates the nominations and recommends fellows for approval by the Packard Foundation Board of Trustees. The Packard Foundation also continues to support fellows as they undertake a variety of self-directed initiatives to support diversity, equity, and inclusion in STEM through additional targeted grants.

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New method uses crowdsourced feedback to help train robots

To teach an AI agent a new task, like how to open a kitchen cabinet, researchers often use reinforcement learning — a trial-and-error process where the agent is rewarded for taking actions that get it closer to the goal.

In many instances, a human expert must carefully design a reward function, which is an incentive mechanism that gives the agent motivation to explore. The human expert must iteratively update that reward function as the agent explores and tries different actions. This can be time-consuming, inefficient, and difficult to scale up, especially when the task is complex and involves many steps.

Researchers from MIT, Harvard University, and the University of Washington have developed a new reinforcement learning approach that doesn’t rely on an expertly designed reward function. Instead, it leverages crowdsourced feedback, gathered from many nonexpert users, to guide the agent as it learns to reach its goal.

While some other methods also attempt to utilize nonexpert feedback, this new approach enables the AI agent to learn more quickly, despite the fact that data crowdsourced from users are often full of errors. These noisy data might cause other methods to fail.

In addition, this new approach allows feedback to be gathered asynchronously, so nonexpert users around the world can contribute to teaching the agent.

“One of the most time-consuming and challenging parts in designing a robotic agent today is engineering the reward function. Today reward functions are designed by expert researchers — a paradigm that is not scalable if we want to teach our robots many different tasks. Our work proposes a way to scale robot learning by crowdsourcing the design of reward function and by making it possible for nonexperts to provide useful feedback,” says Pulkit Agrawal, an assistant professor in the MIT Department of Electrical Engineering and Computer Science (EECS) who leads the Improbable AI Lab in the MIT Computer Science and Artificial Intelligence Laboratory (CSAIL).

In the future, this method could help a robot learn to perform specific tasks in a user’s home quickly, without the owner needing to show the robot physical examples of each task. The robot could explore on its own, with crowdsourced nonexpert feedback guiding its exploration.

“In our method, the reward function guides the agent to what it should explore, instead of telling it exactly what it should do to complete the task. So, even if the human supervision is somewhat inaccurate and noisy, the agent is still able to explore, which helps it learn much better,” explains lead author Marcel Torne ’23, a research assistant in the Improbable AI Lab.

Torne is joined on the paper by his MIT advisor, Agrawal; senior author Abhishek Gupta, assistant professor at the University of Washington; as well as others at the University of Washington and MIT. The research will be presented at the Conference on Neural Information Processing Systems next month.

Noisy feedback

One way to gather user feedback for reinforcement learning is to show a user two photos of states achieved by the agent, and then ask that user which state is closer to a goal. For instance, perhaps a robot’s goal is to open a kitchen cabinet. One image might show that the robot opened the cabinet, while the second might show that it opened the microwave. A user would pick the photo of the “better” state.

Some previous approaches try to use this crowdsourced, binary feedback to optimize a reward function that the agent would use to learn the task. However, because nonexperts are likely to make mistakes, the reward function can become very noisy, so the agent might get stuck and never reach its goal.

“Basically, the agent would take the reward function too seriously. It would try to match the reward function perfectly. So, instead of directly optimizing over the reward function, we just use it to tell the robot which areas it should be exploring,” Torne says.

He and his collaborators decoupled the process into two separate parts, each directed by its own algorithm. They call their new reinforcement learning method HuGE (Human Guided Exploration).

On one side, a goal selector algorithm is continuously updated with crowdsourced human feedback. The feedback is not used as a reward function, but rather to guide the agent’s exploration. In a sense, the nonexpert users drop breadcrumbs that incrementally lead the agent toward its goal.

On the other side, the agent explores on its own, in a self-supervised manner guided by the goal selector. It collects images or videos of actions that it tries, which are then sent to humans and used to update the goal selector.

This narrows down the area for the agent to explore, leading it to more promising areas that are closer to its goal. But if there is no feedback, or if feedback takes a while to arrive, the agent will keep learning on its own, albeit in a slower manner. This enables feedback to be gathered infrequently and asynchronously.

“The exploration loop can keep going autonomously, because it is just going to explore and learn new things. And then when you get some better signal, it is going to explore in more concrete ways. You can just keep them turning at their own pace,” adds Torne.

And because the feedback is just gently guiding the agent’s behavior, it will eventually learn to complete the task even if users provide incorrect answers.

Faster learning

The researchers tested this method on a number of simulated and real-world tasks. In simulation, they used HuGE to effectively learn tasks with long sequences of actions, such as stacking blocks in a particular order or navigating a large maze.

In real-world tests, they utilized HuGE to train robotic arms to draw the letter “U” and pick and place objects. For these tests, they crowdsourced data from 109 nonexpert users in 13 different countries spanning three continents.

In real-world and simulated experiments, HuGE helped agents learn to achieve the goal faster than other methods.

The researchers also found that data crowdsourced from nonexperts yielded better performance than synthetic data, which were produced and labeled by the researchers. For nonexpert users, labeling 30 images or videos took fewer than two minutes.

“This makes it very promising in terms of being able to scale up this method,” Torne adds.

In a related paper, which the researchers presented at the recent Conference on Robot Learning, they enhanced HuGE so an AI agent can learn to perform the task, and then autonomously reset the environment to continue learning. For instance, if the agent learns to open a cabinet, the method also guides the agent to close the cabinet.

“Now we can have it learn completely autonomously without needing human resets,” he says.

The researchers also emphasize that, in this and other learning approaches, it is critical to ensure that AI agents are aligned with human values.

In the future, they want to continue refining HuGE so the agent can learn from other forms of communication, such as natural language and physical interactions with the robot. They are also interested in applying this method to teach multiple agents at once.

This research is funded, in part, by the MIT-IBM Watson AI Lab.

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Search algorithm reveals nearly 200 new kinds of CRISPR systems

Microbial sequence databases contain a wealth of information about enzymes and other molecules that could be adapted for biotechnology. But these databases have grown so large in recent years that they’ve become difficult to search efficiently for enzymes of interest.

Now, scientists at the McGovern Institute for Brain Research at MIT, the Broad Institute of MIT and Harvard, and the National Center for Biotechnology Information (NCBI) at the National Institutes of Health have developed a new search algorithm that has identified 188 kinds of new rare CRISPR systems in bacterial genomes, encompassing thousands of individual systems. The work appears today in Science.

The algorithm, which comes from the lab of pioneering CRISPR researcher Professor Feng Zhang, uses big-data clustering approaches to rapidly search massive amounts of genomic data. The team used their algorithm, called Fast Locality-Sensitive Hashing-based clustering (FLSHclust) to mine three major public databases that contain data from a wide range of unusual bacteria, including ones found in coal mines, breweries, Antarctic lakes, and dog saliva. The scientists found a surprising number and diversity of CRISPR systems, including ones that could make edits to DNA in human cells, others that can target RNA, and many with a variety of other functions.

The new systems could potentially be harnessed to edit mammalian cells with fewer off-target effects than current Cas9 systems. They could also one day be used as diagnostics or serve as molecular records of activity inside cells.

The researchers say their search highlights an unprecedented level of diversity and flexibility of CRISPR and that there are likely many more rare systems yet to be discovered as databases continue to grow.

“Biodiversity is such a treasure trove, and as we continue to sequence more genomes and metagenomic samples, there is a growing need for better tools, like FLSHclust, to search that sequence space to find the molecular gems,” says Zhang, a co-senior author on the study and the James and Patricia Poitras Professor of Neuroscience at MIT with joint appointments in the departments of Brain and Cognitive Sciences and Biological Engineering. Zhang is also an investigator at the McGovern Institute for Brain Research at MIT, a core institute member at the Broad, and an investigator at the Howard Hughes Medical Institute. Eugene Koonin, a distinguished investigator at the NCBI, is co-senior author on the study as well.

Searching for CRISPR

CRISPR, which stands for clustered regularly interspaced short palindromic repeats, is a bacterial defense system that has been engineered into many tools for genome editing and diagnostics.

To mine databases of protein and nucleic acid sequences for novel CRISPR systems, the researchers developed an algorithm based on an approach borrowed from the big data community. This technique, called locality-sensitive hashing, clusters together objects that are similar but not exactly identical. Using this approach allowed the team to probe billions of protein and DNA sequences — from the NCBI, its Whole Genome Shotgun database, and the Joint Genome Institute — in weeks, whereas previous methods that look for identical objects would have taken months. They designed their algorithm to look for genes associated with CRISPR.

“This new algorithm allows us to parse through data in a time frame that’s short enough that we can actually recover results and make biological hypotheses,” says Soumya Kannan PhD ’23, who is a co-first author on the study. Kannan was a graduate student in Zhang’s lab when the study began and is currently a postdoc and Junior Fellow at Harvard University. Han Altae-Tran PhD ’23, a graduate student in Zhang’s lab during the study and currently a postdoc at the University of Washington, was the study’s other co-first author.

“This is a testament to what you can do when you improve on the methods for exploration and use as much data as possible,” says Altae-Tran. “It’s really exciting to be able to improve the scale at which we search.”

New systems

In their analysis, Altae-Tran, Kannan, and their colleagues noticed that the thousands of CRISPR systems they found fell into a few existing and many new categories. They studied several of the new systems in greater detail in the lab.

They found several new variants of known Type I CRISPR systems, which use a guide RNA that is 32 base pairs long rather than the 20-nucleotide guide of Cas9. Because of their longer guide RNAs, these Type I systems could potentially be used to develop more precise gene-editing technology that is less prone to off-target editing. Zhang’s team showed that two of these systems could make short edits in the DNA of human cells. And because these Type I systems are similar in size to CRISPR-Cas9, they could likely be delivered to cells in animals or humans using the same gene-delivery technologies being used today for CRISPR.

One of the Type I systems also showed “collateral activity” — broad degradation of nucleic acids after the CRISPR protein binds its target. Scientists have used similar systems to make infectious disease diagnostics such as SHERLOCK, a tool capable of rapidly sensing a single molecule of DNA or RNA. Zhang’s team thinks the new systems could be adapted for diagnostic technologies as well.

The researchers also uncovered new mechanisms of action for some Type IV CRISPR systems, and a Type VII system that precisely targets RNA, which could potentially be used in RNA editing. Other systems could potentially be used as recording tools — a molecular document of when a gene was expressed — or as sensors of specific activity in a living cell.

Mining data

The scientists say their algorithm could aid in the search for other biochemical systems. “This search algorithm could be used by anyone who wants to work with these large databases for studying how proteins evolve or discovering new genes,” Altae-Tran says.

The researchers add that their findings illustrate not only how diverse CRISPR systems are, but also that most are rare and only found in unusual bacteria. “Some of these microbial systems were exclusively found in water from coal mines,” Kannan says. “If someone hadn’t been interested in that, we may never have seen those systems. Broadening our sampling diversity is really important to continue expanding the diversity of what we can discover.”

This work was supported by the Howard Hughes Medical Institute; the K. Lisa Yang and Hock E. Tan Molecular Therapeutics Center at MIT; Broad Institute Programmable Therapeutics Gift Donors; The Pershing Square Foundation, William Ackman and Neri Oxman; James and Patricia Poitras; BT Charitable Foundation; Asness Family Foundation; Kenneth C. Griffin; the Phillips family; David Cheng; and Robert Metcalfe.

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