Nature Climate Change, Published online: 10 September 2025; doi:10.1038/s41558-025-02417-8

The authors use 1,603 estimates of local extinctions from 1980 to 2021 to show that dragonfly species with wing ornamentation have disproportionately gone extinct and lost habitat because of climate change and wildfire. This highlights the important role of mating traits in species survival under change.

EFF Launches Search for Successor to ‘Visionary Lawyer and Leader’

SAN FRANCISCO – Electronic Frontier Foundation Executive Director Cindy Cohn will step down by mid-2026 after more than 25 years with the organization and a decade as its top officer leading the fight for digital freedoms. 

EFF – defending digital privacy, free speech, and innovation since 1990 – is launching a search for Cohn’s successor. 

“It’s been the honor of my life to help EFF grow and become the strong, effective organization it is today, but it’s time to make space for new leadership. I also want to get back into the fight for civil liberties more directly than I can as the executive director of a thriving 125-person organization,” Cohn said. “I’m incredibly proud of all that we’ve built and accomplished. One of our former interns once called EFF the joyful warriors for internet freedom and I have always loved that characterization.” 

“I know EFF’s lawyers, activists and technologists will continue standing up for freedom, justice and innovation whether we’re fighting trolls, bullies, corporate oligarchs, clueless legislators or outright dictators,” she added. 

"Cindy Cohn has been a relentless advocate for the simple proposition that regular people have a fundamental right to privacy online,” said U.S. Sen. Ron Wyden, D-OR. “Her work – defending encryption, opposing warrantless NSA surveillance, and suing major corporations for violating customer privacy – has consistently put her on the side of users and individuals and against powerful entrenched interests. Cindy's steady leadership at EFF will be missed by everyone who believes the First and Fourth Amendments are just as necessary today as they were more than 200 years ago." 

Cohn, 61, first became involved with EFF in 1993, when EFF asked her to serve as the outside lead attorney in Bernstein v. Dept. of Justice, the successful First Amendment challenge to the U.S. export restrictions on cryptography. She served as EFF’s Legal Director as well as its General Counsel from 2000 through 2015, and she has served as Executive Director since then. She also has co-hosted EFF’s award-winning “How to Fix the Internet” podcast, which is about to conclude its sixth season. Her upcoming professional memoir covering her time at EFF, Privacy’s Defender: My Thirty-Year Fight Against Digital Surveillance, will be published in spring 2026 by MIT Press.  

Cohn was named to TheNonProfitTimes 2020 Power & Influence TOP 50. In 2018, Forbes included her as one of America's Top 50 Women in Tech. The National Law Journal named her one of the 100 most influential lawyers in America in 2013, noting: "[I]f Big Brother is watching, he better look out for Cindy Cohn." That publication also named her in 2006 for "rushing to the barricades wherever freedom and civil liberties are at stake online." In 2007, the National Law Journal named her one of the 50 most influential women lawyers in America.  

In 2010 the Intellectual Property Section of the State Bar of California awarded Cohn its Intellectual Property Vanguard Award and in 2012 the Northern California Chapter of the Society of Professional Journalists awarded her its James Madison Freedom of Information Award. 

Cohn said she made the decision to step down more than a year ago, and later informed EFF’s Board of Directors and executive staff. The Board of Directors has assembled a search committee, which in turn has engaged leadership advisory firm Russell Reynolds Associates to conduct a search for EFF’s new executive director. Inquiries about the search can be directed to EFF@russellreynolds.com.  

The search committee hopes to hire someone next spring, with Cohn planning to remain at EFF for a transition period through early summer.  

“Simply put, Cindy Cohn is an EFF institution,” said Gigi Sohn, chair of EFF’s Board of Directors. “Under her leadership, the organization has grown tremendously, cementing its role as the premier defender of digital privacy, free speech and innovation in the U.S., and perhaps the world. The EFF Board thanks Cindy for her many years of service to EFF, first as Legal Director and for the past 10 years as Executive Director, as well as her willingness to help the organization through this leadership transition. We wish her all the best in her future endeavors, which undoubtedly will be equally as, if not more, successful.” 

“Cindy has been a huge part of EFF’s 35-year history and growth, and the organization simply wouldn’t be where it is today - at the forefront of defending civil liberties in the digital world - without her,” said EFF co-founder Mitch Kapor. “Her strong, compassionate leadership has set a clear and impactful road map for EFF’s work for years to come.” 

“Cindy Cohn is a visionary lawyer and leader who has helped make EFF the world’s foremost digital rights organization,” said American Civil Liberties Union Deputy Legal Director Ben Wizner. “She has also been a dear friend and mentor to so many of us, leading with her warmth and humor as much as her brilliance. I’m excited to see her next act and confident she’ll find new strategies for protecting our rights and liberties.” 

“Cindy is a force in the digital rights community,” said Center for Democracy & Technology President and CEO Alexandra Reeve Givens. “Her visionary leadership has pushed the field forward, championing the rights of individual users and innovators in a fast-changing digital world. Cindy is a tireless advocate for user privacy, free expression, and ensuring technology serves the public good. Her legacy at EFF stands not just in the policy battles and complex cases she’s won, but in the foundation she has built for the next generation of digital rights defenders.” 

For more about Cindy Cohn, with hi-res photo: https://www.eff.org/about/staff/cindy-cohn 

Contact:  JoshRichmanCommunications Directorjrichman@eff.org

Seven technologies developed at MIT Lincoln Laboratory, either wholly or with collaborators, have earned 2025 R&D 100 Awards. This annual awards competition recognizes the year's most significant new technologies, products, and materials available on the marketplace or transitioned to use. An independent panel of technology experts and industry professionals selects the winners.

"Winning an R&D 100 Award is a recognition of the exceptional creativity and effort of our scientists and engineers. The awarded technologies reflect Lincoln Laboratory's mission to transform innovative ideas into real-world solutions for U.S. national security, industry, and society," says Melissa Choi, director of Lincoln Laboratory.

Lincoln Laboratory's winning technologies enhance national security in a range of ways, from securing satellite communication links and identifying nearby emitting devices to providing a layer of defense for U.S. Army vehicles and protecting service members from chemical threats. Other technologies are pushing frontiers in computing, enabling the 3D integration of chips and the close inspection of superconducting electronics. Industry is also benefiting from these developments — for example, by adopting an architecture that streamlines the development of laser communications terminals.

The online publication R&D World manages the awards program. Recipients span Fortune 500 companies, federally funded research institutions, academic and government labs, and small companies. Since 2010, Lincoln Laboratory has received 108 R&D 100 Awards.

Protecting lives 

Tactical Optical Spherical Sensor for Interrogating Threats (TOSSIT) is a throwable, baseball-sized sensor that remotely detects hazardous vapors and aerosols. It is designed to alert soldiers, first responders, and law enforcement to the presence of chemical threats, like nerve and blister agents, industrial chemical accidents, or fentanyl dust. Users can simply toss, drone-drop, or launch TOSSIT into an area of concern. To detect specific chemicals, the sensor samples the air with a built-in fan and uses an internal camera to observe color changes on a removable dye card. If chemicals are present, TOSSIT alerts users wirelessly on an app or via audible, light-up, or vibrational alarms in the sensor.

"TOSSIT fills an unmet need for a chemical-vapor point sensor, one that senses the immediate environment around it, that can be kinetically deployed ahead of service personnel. It provides a low-cost sensing option for vapors and solid aerosol threats — think toxic dust particles — that would otherwise not be detectable by small deployed sensor systems,” says principal investigator Richard Kingsborough. TOSSIT has been tested extensively in the field and is currently being transferred to the military. 

Wideband Selective Propagation Radar (WiSPR) is an advanced radar and communications system developed to protect U.S. Army armored vehicles. The system's active electronically scanned antenna array extends signal range at millimeter-wave frequencies, steering thousands of beams per second to detect incoming kinetic threats while enabling covert communications between vehicles. WiSPR is engineered to have a low probability of detection, helping U.S. Army units evade adversaries seeking to detect radio-frequency (RF) energy emitting from radars. The system is currently in production.

"Current global conflicts are highlighting the susceptibility of armored vehicles to adversary anti-tank weapons. By combining custom technologies and commercial off-the-shelf hardware, the Lincoln Laboratory team produced a WiSPR prototype as quickly and efficiently as possible," says program manager Christopher Serino, who oversaw WiSPR development with principal investigator David Conway.

Advancing computing

Bumpless Integration of Chiplets to Al-Optimized Fabric is an approach that enables the fabrication of next-generation 2D, 2.5D, and 3D integrated circuits. As data-processing demands increase, designers are exploring 3D stacked assemblies of small specialized chips (chiplets) to pack more power into devices. Tiny bumps of conductive material are used to electrically connect these stacks, but these microbumps cannot accommodate the extremely dense, massively interconnected components needed for future microcomputers. To address this issue, Lincoln Laboratory developed a technique eliminating microbumps. Key to this technique is a lithographically produced fabric allowing electrical bonding of chiplet stack layers. Researchers used an AI-driven decision-tree approach to optimize the design of this fabric. This bumpless feature can integrate hundreds of chiplets that perform like a single chip, improving data-processing speed and power efficiency, especially for high-performance AI applications.

"Our novel, bumpless, heterogeneous chiplet integration is a transformative approach addressing two semiconductor industry challenges: expanding chip yield and reducing cost and time to develop systems," says principal investigator Rabindra Das.

Quantum Diamond Magnetic Cryomicroscope is a breakthrough in magnetic field imaging for characterizing superconducting electronics, a promising frontier in high-performance computing. Unlike traditional techniques, this system delivers fast, wide-field, high-resolution imaging at the cryogenic temperatures required for superconducting devices. The instrument combines an optical microscopy system with a cryogenic sensor head containing a diamond engineered with nitrogen-vacancy centers — atomic-scale defects highly sensitive to magnetic fields. The cryomicroscope enables researchers to directly visualize trapped magnetic vortices that interfere with critical circuit components, helping to overcome a major obstacle to scaling superconducting electronics.

“The cryomicroscope gives us an unprecedented window into magnetic behavior in superconducting devices, accelerating progress toward next-generation computing technologies,” says Pauli Kehayias, joint principal investigator with Jennifer Schloss. The instrument is currently advancing superconducting electronics development at Lincoln Laboratory and is poised to impact materials science and quantum technology more broadly.

Enhancing communications 

Lincoln Laboratory Radio Frequency Situational Awareness Model (LL RF-SAM) utilizes advances in AI to enhance U.S. service members' vigilance over the electromagnetic spectrum. The modern spectrum can be described as a swamp of mixed signals originating from civilian, military, or enemy sources. In near-real time, LL RF-SAM inspects these signals to disentangle and identify nearby waveforms and their originating devices. For example, LL RF-SAM can help a user identify a particular packet of energy as a drone transmission protocol and then classify whether that drone is part of a corpus of friendly or enemy drones.

"This type of enhanced context helps military operators make data-driven decisions. The future adoption of this technology will have profound impact across communications, signals intelligence, spectrum management, and wireless infrastructure security," says principal investigator Joey Botero. 

Modular, Agile, Scalable Optical Terminal (MAScOT) is a laser communications (lasercom) terminal architecture that facilitates mission-enabling lasercom solutions adaptable to various space platforms and operating environments. Lasercom is rapidly becoming the go-to technology for space-to-space links in low Earth orbit because of its ability to support significantly higher data rates compared to radio frequency terminals. However, it has yet to be used operationally or commercially for longer-range space-to-ground links, as such systems often require custom designs for specific missions. MASCOT's modular, agile, and scalable design streamlines the process for building lasercom terminals suitable for a range of missions, from near Earth to deep space. MAScOT made its debut on the International Space Station in 2023 to demonstrate NASA's first two-way lasercom relay system, and is now being prepared to serve in an operational capacity on Artemis II, NASA's moon flyby mission scheduled for 2026. Two industry-built terminals have adopted the MAScOT architecture, and technology transfer to additional industry partners is ongoing.

"MAScOT is the latest lasercom terminal designed by Lincoln Laboratory engineers following decades of pioneering lasercom work with NASA, and it is poised to support lasercom for decades to come," says Bryan Robinson, who co-led MAScOT development with Tina Shih. 

Protected Anti-jam Tactical SATCOM (PATS) Key Management System (KMS) Prototype addresses the critical challenge of securely distributing cryptographic keys for military satellite communications (SATCOM) during terminal jamming, compromise, or disconnection. Realizing the U.S. Space Systems Command's vision for resilient, protected tactical SATCOM, the PATS KMS Prototype leverages innovative, bandwidth-efficient protocols and algorithms to enable real-time, scalable key distribution over wireless links, even under attack, so that warfighters can communicate securely in contested environments. PATS KMS is now being adopted as the core of the Department of Defense's next-generation SATCOM architecture.

"PATS KMS is not just a technology — it's a linchpin enabler of resilient, modern SATCOM, built for the realities of today's contested battlefield. We worked hand-in-hand with government stakeholders, operational users, and industry partners across a multiyear, multiphase journey to bring this capability to life," says Joseph Sobchuk, co-principal investigator with Nancy List. The R&D 100 Award is shared with the U.S. Space Force Space Systems Command, whose “visionary leadership has been instrumental in shaping the future of protected tactical SATCOM,” Sobchuk adds.

When cells are healthy, we don’t expect them to suddenly change cell types. A skin cell on your hand won’t naturally morph into a brain cell, and vice versa. That’s thanks to epigenetic memory, which enables the expression of various genes to “lock in” throughout a cell’s lifetime. Failure of this memory can lead to diseases, such as cancer.

Traditionally, scientists have thought that epigenetic memory locks genes either “on” or “off” — either fully activated or fully repressed, like a permanent Lite-Brite pattern. But MIT engineers have found that the picture has many more shades.

In a new study appearing today in Cell Genomics, the team reports that a cell’s memory is set not by on/off switching but through a more graded, dimmer-like dial of gene expression.

The researchers carried out experiments in which they set the expression of a single gene at different levels in different cells. While conventional wisdom would assume the gene should eventually switch on or off, the researchers found that the gene’s original expression persisted: Cells whose gene expression was set along a spectrum between on and off remained in this in-between state.

The results suggest that epigenetic memory — the process by which cells retain gene expression and “remember” their identity — is not binary but instead analog, which allows for a spectrum of gene expression and associated cell identities.

“Our finding opens the possibility that cells commit to their final identity by locking genes at specific levels of gene expression instead of just on and off,” says study author Domitilla Del Vecchio, professor of mechanical and biological engineering at MIT. “The consequence is that there may be many more cell types in our body than we know and recognize today, that may have important functions and could underlie healthy or diseased states.”

The study’s MIT lead authors are Sebastian Palacios and Simone Bruno, with additional co-authors.

Beyond binary

Every cell shares the same genome, which can be thought of as the starting ingredient for life. As a cell takes shape, it differentiates into one type or another, through the expression of genes in its genome. Some genes are activated, while others are repressed. The combination steers a cell toward one identity versus another.

A process of DNA methylation, by which certain molecules attach to the genes’ DNA, helps lock their expression in place. DNA methylation assists a cell to “remember” its unique pattern of gene expression, which ultimately establishes the cell’s identity.

Del Vecchio’s group at MIT applies mathematics and genetic engineering to understand cellular molecular processes and to engineer cells with new capabilities. In previous work, her group was experimenting with DNA methylation and ways to lock the expression of certain genes in ovarian cells.

“The textbook understanding was that DNA methylation had a role to lock genes in either an on or off state,” Del Vecchio says. “We thought this was the dogma. But then we started seeing results that were not consistent with that.”

While many of the cells in their experiment exhibited an all-or-nothing expression of genes, a significant number of cells appeared to freeze genes in an in-between state — neither entirely on or off.

“We found there was a spectrum of cells that expressed any level between on and off,” Palacios says. “And we thought, how is this possible?”

Shades of blue

In their new study, the team aimed to see whether the in-between gene expression they observed was a fluke or a more established property of cells that until now has gone unnoticed.

“It could be that scientists disregarded cells that don’t have a clear commitment, because they assumed this was a transient state,” Del Vecchio says. “But actually these in-between cell types may be permanent states that could have important functions.”

To test their idea, the researchers ran experiments with hamster ovarian cells — a line of cells commonly used in the laboratory. In each cell, an engineered gene was initially set to a different level of expression. The gene was turned fully on in some cells, completely off in others, and set somewhere in between on and off for the remaining cells.

The team paired the engineered gene with a fluorescent marker that lights up with a brightness corresponding to the gene’s level of expression. The researchers introduced, for a short time, an enzyme that triggers the gene’s DNA methylation, a natural gene-locking mechanism. They then monitored the cells over five months to see whether the modification would lock the genes in place at their in-between expression levels, or whether the genes would migrate toward fully on or off states before locking in.

“Our fluorescent marker is blue, and we see cells glow across the entire spectrum, from really shiny blue, to dimmer and dimmer, to no blue at all,” Del Vecchio says. “Every intensity level is maintained over time, which means gene expression is graded, or analog, and not binary. We were very surprised, because we thought after such a long time, the gene would veer off, to be either fully on or off, but it did not.”

The findings open new avenues into engineering more complex artificial tissues and organs by tuning the expression of certain genes in a cell’s genome, like a dial on a radio, rather than a switch. The results also complicate the picture of how a cell’s epigenetic memory works to establish its identity. It opens up the possibility that cell modifications such as those exhibited in therapy-resistant tumors could be treated in a more precise fashion.

“Del Vecchio and colleagues have beautifully shown how analog memory arises through chemical modifications to the DNA itself,” says Michael Elowitz, professor of biology and biological engineering at the California institute of Technology, who was not involved in the study. “As a result, we can now imagine repurposing this natural analog memory mechanism, invented by evolution, in the field of synthetic biology, where it could help allow us to program permanent and precise multicellular behaviors.”

“One of the things that enables the complexity in humans is epigenetic memory,” Palacios says. “And we find that it is not what we thought. For me, that’s actually mind-blowing. And I think we’re going to find that this analog memory is relevant for many different processes across biology.”

This research was supported, in part, by the National Science Foundation, MODULUS, and a Vannevar Bush Faculty Fellowship through the U.S. Office of Naval Research.

A couple of months ago, a new paper demonstrated some new attacks against the Fiat-Shamir transformation. Quanta published a good article that explains the results.

This is a pretty exciting paper from a theoretical perspective, but I don’t see it leading to any practical real-world cryptanalysis. The fact that there are some weird circumstances that result in Fiat-Shamir insecurities isn’t new—many dozens of papers have been published about it since 1986. What this new result does is extend this known problem to slightly less weird (but still highly contrived) situations. But it’s a completely different matter to extend these sorts of attacks to “natural” situations...

After meeting with reinsurance companies abroad, the state’s insurance commissioner pushed for new laws to expand property insurance.

The country's explosive growth in wind and solar is moving it toward peak coal and gas, according to new research.

Fiscal 2026 legislation would roll back spending to the lowest level in decades.

The power needs of electric vehicles will compel "investment in new wind, solar, storage, and natural gas capacity," new research finds.

The regional transportation agency is tapping its capital funds to restore routes shortened or canceled amid a budget showdown.

Harvesting specialists say home gardeners can benefit from collecting rain and runoff to irrigate plants.

The financial secretary added that Hong Kong is on track to meet its goal to reduce carbon emissions by 50 percent by 2035.

Many parts of Europe that once saw air conditioning as a U.S. excess are beginning to embrace the idea.

The boost was driven by expectations of higher footfall — and sales — as shoppers sought refuge from Japan’s elevated temperatures.

Using tiny particles shaped like bottlebrushes, MIT chemists have found a way to deliver a large range of chemotherapy drugs directly to tumor cells.

To guide them to the right location, each particle contains an antibody that targets a specific tumor protein. This antibody is tethered to bottlebrush-shaped polymer chains carrying dozens or hundreds of drug molecules — a much larger payload than can be delivered by any existing antibody-drug conjugates.

In mouse models of breast and ovarian cancer, the researchers found that treatment with these conjugated particles could eliminate most tumors. In the future, the particles could be modified to target other types of cancer, by swapping in different antibodies.

“We are excited about the potential to open up a new landscape of payloads and payload combinations with this technology, that could ultimately provide more effective therapies for cancer patients,” says Jeremiah Johnson, the A. Thomas Geurtin Professor of Chemistry at MIT, a member of the Koch Institute for Integrative Cancer Research, and the senior author of the new study.

MIT postdoc Bin Liu is the lead author of the paper, which appears today in Nature Biotechnology.

A bigger drug payload

Antibody-drug conjugates (ADCs) are a promising type of cancer treatment that consist of a cancer-targeting antibody attached to a chemotherapy drug. At least 15 ADCs have been approved by the FDA to treat several different types of cancer.

This approach allows specific targeting of a cancer drug to a tumor, which helps to prevent some of the side effects that occur when chemotherapy drugs are given intravenously. However, one drawback to currently approved ADCs is that only a handful of drug molecules can be attached to each antibody. That means they can only be used with very potent drugs — usually DNA-damaging agents or drugs that interfere with cell division.

To try to use a broader range of drugs, which are often less potent, Johnson and his colleagues decided to adapt bottlebrush particles that they had previously invented. These particles consist of a polymer backbone that are attached to tens to hundreds of “prodrug” molecules — inactive drug molecules that are activated upon release within the body. This structure allows the particles to deliver a wide range of drug molecules, and the particles can be designed to carry multiple drugs in specific ratios.

Using a technique called click chemistry, the researchers showed that they could attach one, two, or three of their bottlebrush polymers to a single tumor-targeting antibody, creating an antibody-bottlebrush conjugate (ABC). This means that just one antibody can carry hundreds of prodrug molecules. The currently approved ADCs can carry a maximum of about eight drug molecules.

The huge number of payloads in the ABC particles allows the researchers to incorporate less potent cancer drugs such as doxorubicin or paclitaxel, which enhances the customizability of the particles and the variety of drug combinations that can be used.

“We can use antibody-bottlebrush conjugates to increase the drug loading, and in that case, we can use less potent drugs,” Liu says. “In the future, we can very easily copolymerize with multiple drugs together to achieve combination therapy.”

The prodrug molecules are attached to the polymer backbone by cleavable linkers. After the particles reach a tumor site, some of these linkers are broken right away, allowing the drugs to kill nearby cancer cells even if they don’t express the target antibody. Other particles are absorbed into cells with the target antibody before releasing their toxic payload.

Effective treatment

For this study, the researchers created ABC particles carrying a few different types of drugs: microtubule inhibitors called MMAE and paclitaxel, and two DNA-damaging agents, doxorubicin and SN-38. They also designed ABC particles carrying an experimental type of drug known as PROTAC (proteolysis-targeting chimera), which can selectively degrade disease-causing proteins inside cells.

Each bottlebrush was tethered to an antibody targeting either HER2, a protein often overexpressed in breast cancer, or MUC1, which is commonly found in ovarian, lung, and other types of cancer.

The researchers tested each of the ABCs in mouse models of breast or ovarian cancer and found that in most cases, the ABC particles were able to eradicate the tumors. This treatment was significantly more effective than giving the same bottlebrush prodrugs by injection, without being conjugated to a targeting antibody.

“We used a very low dose, almost 100 times lower compared to the traditional small-molecule drug, and the ABC still can achieve much better efficacy compared to the small-molecule drug given on its own,” Liu says.

These ABCs also performed better than two FDA-approved ADCs, T-DXd and TDM-1, which both use HER2 to target cells. T-DXd carries deruxtecan, which interferes with DNA replication, and TDM-1 carries emtansine, a microtubule inhibitor.

In future work, the MIT team plans to try delivering combinations of drugs that work by different mechanisms, which could enhance their overall effectiveness. Among these could be immunotherapy drugs such as STING activators.

The researchers are also working on swapping in different antibodies, such as antibodies targeting EGFR, which is widely expressed in many tumors. More than 100 antibodies have been approved to treat cancer and other diseases, and in theory any of those could be conjugated to cancer drugs to create a targeted therapy.

The research was funded in part by the National Institutes of Health, the Ludwig Center at MIT, and the Koch Institute Frontier Research Program. 

Nature Climate Change, Published online: 09 September 2025; doi:10.1038/s41558-025-02420-z

Africa’s future climate could be shaped by solar radiation management (SRM) decisions made elsewhere. To ensure these technologies, if ever pursued, reflect principles of justice and local priorities, Africa must move from passive recipient to active leader in SRM research, governance and public engagement.

Nature Climate Change, Published online: 09 September 2025; doi:10.1038/s41558-025-02419-6

The authors combine tracking and body mass data from five migratory waterfowl species to understand their capacity to accelerate migration in response to earlier spring. They show considerable scope for faster migration by reducing the fuelling time before departure and subsequently on stopovers

The Whitehead Institute for Biomedical Research fondly remembers its founding director, David Baltimore, a former MIT Institute Professor and Nobel laureate who died Sept. 6 at age 87.

With discovery after discovery, Baltimore brought to light key features of biology with direct implications for human health. His work at MIT earned him a share of the 1975 Nobel Prize in Physiology or Medicine (along with Howard Temin and Renato Dulbecco) for discovering reverse transcriptase and identifying retroviruses, which use RNA to synthesize viral DNA.

Following the award, Baltimore reoriented his laboratory’s focus to pursue a mix of immunology and virology. Among the lab’s most significant subsequent discoveries were the identification of a pair of proteins that play an essential role in enabling the immune system to create antibodies for so many different molecules, and investigations into how certain viruses can cause cell transformation and cancer. Work from Baltimore’s lab also helped lead to the development of the important cancer drug Gleevec — the first small molecule to target an oncoprotein inside of cells.

In 1982, Baltimore partnered with philanthropist Edwin C. “Jack” Whitehead to conceive and launch the Whitehead Institute and then served as its founding director until 1990. Within a decade of its founding, the Baltimore-led Whitehead Institute was named the world’s top research institution in molecular biology and genetics.

“More than 40 years later, Whitehead Institute is thriving, still guided by the strategic vision that David Baltimore and Jack Whitehead articulated,” says Phillip Sharp, MIT Institute Professor Emeritus, former Whitehead board member, and fellow Nobel laureate. “Of all David’s myriad and significant contributions to science, his role in building the first independent biomedical research institute associated with MIT and guiding it to extraordinary success may well prove to have had the broadest and longest-term impact.” 

Ruth Lehmann, director and president of the Whitehead Institute, and professor of biology at MIT, says: “I, like many others, owe my career to David Baltimore. He recruited me to Whitehead Institute and MIT in 1988 as a faculty member, taking a risk on an unproven, freshly-minted PhD graduate from Germany. As director, David was incredibly skilled at bringing together talented scientists at different stages of their careers and facilitating their collaboration so that the whole would be greater than the sum of its parts. This approach remains a core strength of Whitehead Institute.”

As part of the Whitehead Institute’s mission to cultivate the next generation of scientific leaders, Baltimore founded the Whitehead Fellows program, which provides extraordinarily talented recent PhD and MD graduates with the opportunity to launch their own labs, rather than to go into traditional postdoctoral positions. The program has been a huge success, with former fellows going on to excel as leaders in research, education, and industry.

David Page, MIT professor of biology, Whitehead Institute member, and former director who was the Whitehead's first fellow, recalls, “David was both an amazing scientist and a peerless leader of aspiring scientists. The launching of the Whitehead Fellows program reflected his recipe for institutional success: gather up the resources to allow young scientists to realize their dreams, recruit with an eye toward potential for outsized impact, and quietly mentor and support without taking credit for others’ successes — all while treating junior colleagues as equals. It is a beautiful strategy that David designed and executed magnificently.”

Sally Kornbluth, president of MIT and a member of the Whitehead Institute Board of Directors, says that “David was a scientific hero for so many. He was one of those remarkable individuals who could make stellar scientific breakthroughs and lead major institutions with extreme thoughtfulness and grace. He will be missed by the whole scientific community.”

“David was a wise giant. He was brilliant. He was an extraordinarily effective, ethical leader and institution builder who influenced and inspired generations of scientists and premier institutions,” says Susan Whitehead, member of the board of directors and daughter of Jack Whitehead.

Gerald R. Fink, the Margaret and Herman Sokol Professor Emeritus at MIT who was recruited by Baltimore from Cornell University as one of four founding members of the Whitehead Institute, and who succeeded him as director in 1990, observes: “David became my hero and friend. He upheld the highest scientific ideals and instilled trust and admiration in all around him.”

     David Baltimore - Infinite History (2010)
     Video: MIT | Watch with transcript

Baltimore was born in New York City in 1938. His scientific career began at Swarthmore College, where he earned a bachelor’s degree with high honors in chemistry in 1960. He then began doctoral studies in biophysics at MIT, but in 1961 shifted his focus to animal viruses and moved to what is now the Rockefeller University, where he did his thesis work in the lab of Richard Franklin.

After completing postdoctoral fellowships with James Darnell at MIT and Jerard Hurwitz at the Albert Einstein College of Medicine, Baltimore launched his own lab at the Salk Institute for Biological Studies from 1965 to 1968. Then, in 1968, he returned to MIT as a member of its biology faculty, where he remained until 1990. (Whitehead Institute’s members hold parallel appointments as faculty in the MIT Department of Biology.)

In 1990, Baltimore left the Whitehead Institute and MIT to become the president of Rockefeller University. He returned to MIT from 1994 to 1997, serving as an Institute Professor, after which he was named president of Caltech. Baltimore held that position until 2006, when he was elected to a three-year term as president of the American Association for the Advancement of Science.

For decades, Baltimore has been viewed not just as a brilliant scientist and talented academic leader, but also as a wise counsel to the scientific community. For example, he helped organize the 1975 Asilomar Conference on Recombinant DNA, which created stringent safety guidelines for the study and use of recombinant DNA technology. He played a leadership role in the development of policies on AIDS research and treatment, and on genomic editing. Serving as an advisor to both organizations and individual scientists, he helped to shape the strategic direction of dozens of institutions and to advance the careers of generations of researchers. As Founding Member Robert Weinberg summarizes it, “He had no tolerance for nonsense and weak science.”  

In 2023, the Whitehead Institute established the endowed David Baltimore Chair in Biomedical Research, honoring Baltimore’s six decades of scientific, academic, and policy leadership and his impact on advancing innovative basic biomedical research.

“David was a visionary leader in science and the institutions that sustain it. He devoted his career to advancing scientific knowledge and strengthening the communities that make discovery possible, and his leadership of Whitehead Institute exemplified this,” says Richard Young, MIT professor of biology and Whitehead Institute member. “David approached life with keen observation, boundless curiosity, and a gift for insight that made him both a brilliant scientist and a delightful companion. His commitment to mentoring and supporting young scientists left a lasting legacy, inspiring the next generation to pursue impactful contributions to biomedical research. Many of us found in him not only a mentor and role model, but also a steadfast friend whose presence enriched our lives and whose absence will be profoundly felt.”

Most people recognize Alzheimer’s disease from its devastating symptoms such as memory loss, while new drugs target pathological aspects of disease manifestations, such as plaques of amyloid proteins. Now, a sweeping new open-access study in the Sept. 4 edition of Cell by MIT researchers shows the importance of understanding the disease as a battle over how well brain cells control the expression of their genes. The study paints a high-resolution picture of a desperate struggle to maintain healthy gene expression and gene regulation, where the consequences of failure or success are nothing less than the loss or preservation of cell function and cognition.

The study presents a first-of-its-kind, multimodal atlas of combined gene expression and gene regulation spanning 3.5 million cells from six brain regions, obtained by profiling 384 post-mortem brain samples across 111 donors. The researchers profiled both the “transcriptome,” showing which genes are expressed into RNA, and the “epigenome,” the set of chromosomal modifications that establish which DNA regions are accessible and thus utilized between different cell types.

The resulting atlas revealed many insights showing that the progression of Alzheimer’s is characterized by two major epigenomic trends. The first is that vulnerable cells in key brain regions suffer a breakdown of the rigorous nuclear “compartments” they normally maintain to ensure some parts of the genome are open for expression but others remain locked away. The second major finding is that susceptible cells experience a loss of “epigenomic information,” meaning they lose their grip on the unique pattern of gene regulation and expression that gives them their specific identity and enables their healthy function.

Accompanying the evidence of compromised compartmentalization and the erosion of epigenomic information are many specific findings pinpointing molecular circuitry that breaks down by cell type, by region, and gene network. They found, for instance, that when epigenomic conditions deteriorate, that opens the door to expression of many genes associated with disease, whereas if cells manage to keep their epigenomic house in order, they can keep disease-associated genes in check. Moreover, the researchers clearly saw that when the epigenomic breakdowns were occurring people lost cognitive ability, but where epigenomic stability remained, so did cognition.

“To understand the circuitry, the logic responsible for gene expression changes in Alzheimer’s disease [AD], we needed to understand the regulation and upstream control of all the changes that are happening, and that’s where the epigenome comes in,” says senior author Manolis Kellis, a professor in the Computer Science and Artificial Intelligence Lab and head of MIT’s Computational Biology Group. “This is the first large-scale, single-cell, multi-region gene-regulatory atlas of AD, systematically dissecting the dynamics of epigenomic and transcriptomic programs across disease progression and resilience.”

By providing that detailed examination of the epigenomic mechanisms of Alzheimer’s progression, the study provides a blueprint for devising new Alzheimer’s treatments that can target factors underlying the broad erosion of epigenomic control or the specific manifestations that affect key cell types such as neurons and supporting glial cells.

“The key to developing new and more effective treatments for Alzheimer’s disease depends on deepening our understanding of the mechanisms that contribute to the breakdowns of cellular and network function in the brain,” says Picower Professor and co-corresponding author Li-Huei Tsai, director of The Picower Institute for Learning and Memory and a founding member of MIT’s Aging Brain Initiative, along with Kellis. “This new data advances our understanding of how epigenomic factors drive disease.”

Kellis Lab members Zunpeng Liu and Shanshan Zhang are the study’s co-lead authors.

Compromised compartments and eroded information

Among the post-mortem brain samples in the study, 57 came from donors to the Religious Orders Study or the Rush Memory and Aging Project (collectively known as “ROSMAP”) who did not have AD pathology or symptoms, while 33 came from donors with early-stage pathology and 21 came from donors at a late stage. The samples therefore provided rich information about the symptoms and pathology each donor was experiencing before death.

In the new study, Liu and Zhang combined analyses of single-cell RNA sequencing of the samples, which measures which genes are being expressed in each cell, and ATACseq, which measures whether chromosomal regions are accessible for gene expression. Considered together, these transcriptomic and epigenomic measures enabled the researchers to understand the molecular details of how gene expression is regulated across seven broad classes of brain cells (e.g., neurons or other glial cell types) and 67 subtypes of cell types (e.g., 17 kinds of excitatory neurons or six kinds of inhibitory ones).

The researchers annotated more than 1 million gene-regulatory control regions that different cells employ to establish their specific identities and functionality using epigenomic marking. Then, by comparing the cells from Alzheimer’s brains to the ones without, and accounting for stage of pathology and cognitive symptoms, they could produce rigorous associations between the erosion of these epigenomic markings, and ultimately loss of function.

For instance, they saw that among people who advanced to late-stage AD, normally repressive compartments opened up for more expression and compartments that were normally more open during health became more repressed. Worryingly, when the normally repressive compartments of brain cells opened up, they became more afflicted with disease.

“For Alzheimer’s patients, repressive compartments opened up, and gene expression levels increased, which was associated with decreased cognitive function,” explains Liu.

But when cells managed to keep their compartments in order such that they expressed the genes they were supposed to, people remained cognitively intact.

Meanwhile, based on the cells’ expression of their regulatory elements, the researchers created an epigenomic information score for each cell. Generally, information declined as pathology progressed, but that was particularly notable among cells in the two brain regions affected earliest in Alzheimer’s: the entorhinal cortex and the hippocampus. The analyses also highlighted specific cell types that were especially vulnerable including microglia that play immune and other roles, oligodendrocytes that produce myelin insulation for neurons, and particular kinds of excitatory neurons.

Risk genes and “chromatin guardians”

Detailed analyses in the paper highlighted how epigenomic regulation tracked with disease-related problems, Liu notes. The e4 variant of the APOE gene, for instance, is widely understood to be the single biggest genetic risk factor for Alzheimer’s. In APOE4 brains, microglia initially responded to the emerging disease pathology with an increase in their epigenomic information, suggesting that they were stepping up to their unique responsibility to fight off disease. But as the disease progressed, the cells exhibited a sharp drop off in information, a sign of deterioration and degeneration. This turnabout was strongest in people who had two copies of APOE4, rather than just one. The findings, Kellis said, suggest that APOE4 might destabilize the genome of microglia, causing them to burn out.

Another example is the fate of neurons expressing the gene RELN and its protein Reelin. Prior studies, including by Kellis and Tsai, have shown that RELN- expressing neurons in the entorhinal cortex and hippocampus are especially vulnerable in Alzheimer’s, but promote resilience if they survive. The new study sheds new light on their fate by demonstrating that they exhibit early and severe epigenomic information loss as disease advances, but that in people who remained cognitively resilient the neurons maintained epigenomic information.

In yet another example, the researchers tracked what they colloquially call “chromatin guardians” because their expression sustains and regulates cells’ epigenomic programs. For instance, cells with greater epigenomic erosion and advanced AD progression displayed increased chromatin accessibility in areas that were supposed to be locked down by Polycomb repression genes or other gene expression silencers. While resilient cells expressed genes promoting neural connectivity, epigenomically eroded cells expressed genes linked to inflammation and oxidative stress.

“The message is clear: Alzheimer’s is not only about plaques and tangles, but about the erosion of nuclear order itself,” Kellis says. “Cognitive decline emerges when chromatin guardians lose ground to the forces of erosion, switching from resilience to vulnerability at the most fundamental level of genome regulation.

“And when our brain cells lose their epigenomic memory marks and epigenomic information at the lowest level deep inside our neurons and microglia, it seems that Alheimer’s patients also lose their memory and cognition at the highest level.”

Other authors of the paper are Benjamin T. James, Kyriaki Galani, Riley J. Mangan, Stuart Benjamin Fass, Chuqian Liang, Manoj M. Wagle, Carles A. Boix, Yosuke Tanigawa, Sukwon Yun, Yena Sung, Xushen Xiong, Na Sun, Lei Hou, Martin Wohlwend, Mufan Qiu, Xikun Han, Lei Xiong, Efthalia Preka, Lei Huang, William F. Li, Li-Lun Ho, Amy Grayson, Julio Mantero, Alexey Kozlenkov, Hansruedi Mathys, Tianlong Chen, Stella Dracheva, and David A. Bennett.

Funding for the research came from the National Institutes of Health, the National Science Foundation, the Cure Alzheimer’s Fund, the Freedom Together Foundation, the Robert A. and Renee E. Belfer Family Foundation, Eduardo Eurnekian, and Joseph P. DiSabato.

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