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School of Science appoints 12 faculty members to named professorships
School of Science
September 11, 2020

The School of Science has awarded chaired appointments to 12 faculty members. These faculty, who are members of the departments of Biology; Brain and Cognitive Sciences; Chemistry; Earth, Atmospheric and Planetary Sciences; and Physics, receive additional support to pursue their research and develop their careers.

Kristin Bergmann, an assistant professor in the Department of Earth, Atmospheric and Planetary Sciences, has been named a D. Reid Weedon, Jr. ’41 Career Development Professor. This is a three-year professorship. Bergmann’s research integrates across sedimentology and stratigraphy, geochemistry, and geobiology to reveal aspects of Earth’s ancient environments. She aims to better constrain Earth’s climate record and carbon cycle during the evolution of early eukaryotes, including animals. Most of her efforts involve reconstructing the details of carbonate rocks, which store much of Earth’s carbon, and thus, are an important component of Earth’s climate system over long timescales.

Joseph Checkelscky is an associate professor in the Department of Physics and has been named a Mitsui Career Development Professor in Contemporary Technology, an appointment he will hold until 2023. His research in quantum materials relies on experimental methods at the intersection of physics, chemistry, and nanoscience. This work is aimed toward synthesizing new crystalline systems that manifest their quantum nature on a macroscopic scale. He aims to realize and study these crystalline systems, which can then serve as platforms for next-generation quantum sensors, quantum communication, and quantum computers.

Mircea Dincă, appointed a W. M. Keck Professor of Energy, is a professor in the Department of Chemistry. This appointment has a five-year term. The topic of Dincă’s research falls largely under the umbrella of energy storage and conversion. His interest in applied energy usage involves creating new organic and inorganic materials that can improve the efficiency of energy collection, storage, and generation while decreasing environmental impacts. Recently, he has developed materials for efficient air-conditioning units and been collaborating with Automobili Lamborghini on electric vehicle design.

Matthew Evans has been appointed to a five-year Mathworks Physics Professorship. Evans, a professor in the Department of Physics, focuses on the instruments used to detect gravitational waves. A member of MIT’s Laser Interferometer Gravitational-Wave Observatory (LIGO) research group, he engineers ways to fine-tune the detection capabilities of the massive ground-based facilities that are being used to identify collisions between black holes and stars in deep space. By removing thermal and quantum limitations, he can increase the sensitivity of the device’s measurements and, thus, its scope of exploration. Evans is also a member of the MIT Kavli Institute for Astrophysics and Space Research.

Evelina Fedorenko is an associate professor in the Department of Brain and Cognitive Sciences and has been named a Frederick A. (1971) and Carole J. Middleton Career Development Professor of Neuroscience. Studying how the brain processes language, Fedorenko uses behavioral studies, brain imaging, neurosurgical recording and stimulation, and computational modelling to better grasp language comprehension and production. In her efforts to elucidate how and what parts of the brain support language processing, she evaluates both typical and atypical brains. Fedorenko is an associate member of the McGovern Institute for Brain Research.

Ankur Jain is an assistant professor in the Department of Biology and now a Thomas D. and Virginia W. Cabot Career Development Professor. He will hold this career development appointment for a term of three years. Jain studies how cells organize their contents. Within a cell, there are numerous compartments that form due to weak interactions between biomolecules and exist without an enclosing membrane. By analyzing the biochemistry and biophysics of these compartments, Jain deduces the principles of cellular organization and its dysfunction in human disease. Jain is also a member of the Whitehead Institute for Biomedical Research.

Pulin Li, an assistant professor in the Department of Biology and the Eugene Bell Career Development Professor of Tissue Engineering for the next three years, explores genetic circuitry in building and maintain a tissue. In particular, she investigates how communication circuitry between individual cells can extrapolate into multicellular behavior using both natural and synthetically generated tissues, for which she combines the fields of synthetic and systems biology, biophysics, and bioengineering. A stronger understanding of genetic circuitry could allow for progress in medicine involving embryonic development and tissue engineering. Li is a member of the Whitehead Institute for Biomedical Research.

Elizabeth Nolan, appointed an Ivan R. Cottrell Professor of Immunology, investigates innate immunity and infectious disease. The Department of Chemistry professor, who will hold this chaired professorship for five years, combines experimental chemistry and microbiology to learn about human immune responses to, and interactions with, microbial pathogens. This research includes elucidating the fight between host and pathogen for essential metal nutrients and the functions of host-defense peptides and proteins during infection. With this knowledge, Nolan contributes to fundamental understanding of the host’s ability to combat microbial infection, which may provide new strategies to treat infectious disease.

Leigh “Wiki” Royden is now a Cecil and Ida Green Professor of Geology and Geophysics. The five-year appointment supports her research on the large-scale dynamics and tectonics of the Earth as a professor in the Department of Earth, Atmospheric and Planetary Sciences. Fundamental to geoscience, the tectonics of regional and global systems are closely linked, particularly through the subduction of the plates into the mantle. Royden’s research adds to our understanding a of the structure and dynamics of the crust and the upper portion of the mantle through observation, theory and modeling. This progress has profound implications for global natural events, like mountain building and continental break-up.

Phiala Shanahan has been appointed a Class of 1957 Career Development Professor for three years. Shanahan is an assistant professor in the Department of Physics, where she specializes in theoretical and nuclear physics. Shanahan’s research uses supercomputers to provide insight into the structure of protons and nuclei in terms of their quark and gluon constituents. Her work also informs searches for new physics beyond the current Standard Model, such dark matter. She is a member of the MIT Center for Theoretical Physics.

Xiao Wang, an assistant professor, has also been named a new Thomas D. and Virginia W. Cabot Professor. In the Department of Chemistry, Wang designs and produces novel methods and tools for analyzing the brain. Integrating chemistry, biophysics, and genomics, her work provides higher-resolution imaging and sampling to explain how the brain functions across molecular to system-wide scales. Wang is also a core member of the Broad Institute of MIT and Harvard.

Bin Zhang has been appointed a Pfizer Inc-Gerald Laubach Career Development Professor for a three-year term. Zhang, an assistant professor in the Department of Chemistry, hopes to connect the framework of the human genome sequence with its various functions on various time and spatial scales. By developing theoretical and computational approaches to categorize information about dynamics, organization, and complexity of the genome, he aims to build a quantitative, predictive modelling tool. This tool could even produce 3D representations of details happening at a microscopic level within the body.

Covid-19 scientific leaders share expertise in new MIT class
Greta Friar | Whitehead Institute
September 9, 2020

As the Covid-19 pandemic swept across the globe, bringing everyday life to a screeching halt, researchers at MIT and its affiliates ramped down much of their lab work and stopped teaching classes in person, but refused to come to a standstill. Instead, they changed tacks and took action investigating the many unknowns of Covid-19 and the virus that causes it (SARS-CoV-2), organizing pandemic responses, and communicating with the public and each other about what they knew.

One result of this period was the advent of a new course, aimed at providing MIT students with information on the science of the pandemic. The MIT Department of Biology tapped two scientists with experience working on pandemics to spearhead a course, 7.00 (COVID-19, SARS-CoV-2 and the Pandemic), which began Sept. 1. Whitehead Institute member and MIT Professor Richard Young, who had been quick to organize Covid-19 related research efforts, and Ragon Institute Associate Director Facundo Batista, a resident expert on immunology and infectious disease, agreed to lead the course.

The class meets virtually on Tuesday mornings, and a public livestream and recordings are available for anyone who wants to watch the lectures. Students who are taking the course for credit also gain access to a weekly session led by Lena Afeyan, a teaching assistant and MIT graduate student in Young’s lab at the Whitehead Institute. The session provides relevant background information on the science before the lectures.

Getting students up to speed on what is and is not known about the pandemic is no easy task. The science is complex and, in these early days, full of unknowns. Experts in many fields must pool their knowledge; virologists, immunologists, epidemiologists, public health researchers, clinicians, and more are focused on important pieces of the puzzle. Therefore, Young and Batista reached out to the leaders in all of those fields to give lectures in the course. Students will hear from experts that include Anthony Fauci, the longtime director of the National Institute of Allergy and Infectious Diseases, as well as David Baltimore of Caltech; Kizzmekia Corbett of the National Institutes of Health; Britt Glaunsinger of the University of California at Berkeley; Akiko Iwasaki of Yale University; Eric Lander of the Broad Institute of MIT and Harvard; Michel Nussenzweig of Rockefeller University; Arlene Sharpe of Harvard Medical School and Brigham and Women’s Hospital; Bruce Walker of the Ragon Institute of Massachusetts General Hospital, MIT, and Harvard; and others at the forefront of Covid-19 efforts. The course faculty agree that the best way to get accurate information to students is to have the experts provide it directly.

Designing the course

For many of the students, Covid-19 may be their first serious encounter with a pandemic, but a number of the lecturers have worked on the AIDS pandemic or other widespread infectious diseases, which they draw on when teaching.

“I like to put the coronavirus in the context of viruses I know better, like flu and HIV and polio virus,” says David Baltimore, the Nobel laureate professor of biology and president emeritus at Caltech who was previously the first director of the Whitehead Institute and a professor at MIT. However, the scientists’ relevant backgrounds can only help so much. The new coronavirus is a unique and difficult research subject.

“It has no obvious evolutionary relationship to other viruses. It’s got a much longer RNA, many more genes, so more complexity of function, more complexity of genetics, and it’s received relatively little study up until recently,” Baltimore says. “There is a lot more work that needs to be done.”

When planning the class, Young wanted to give all of the information needed to understand what is likely the first pandemic to powerfully impact the lives of the undergraduates taking the course. His motives were pedagogical — and practical.

“If we give people knowledge of what’s known and not known about the virus, provided by experts whom they trust, they can help us come up with solutions,” Young says.

Young and Batista expect that some of their students will soon be conducting their own Covid-19 research. Batista hopes that this experience will encourage students to think even beyond the scope of the current pandemic.

“I think the U.S. and the Western world have underestimated the risk of infectious diseases because the big pandemics have been happening elsewhere. This class is about bringing people together on Covid-19, and more than that, [it is about] creating a consciousness about the threat of future infections,” Batista says.

Where to start?

The first lecture was given by Bruce Walker, director of the Ragon Institute. Walker provided an overview of the available information, including how the pandemic appears to have started, how the virus causes disease, and what the prospects are for treatment and vaccines. The level of the science is aimed at MIT undergraduates, but because the livestream audience may have different science backgrounds, Walker made sure to define basic terms and concepts as he went. The lecture was attended by 250 students, with more than 7,000 people watching the livestream.

Registered students can ask questions during a Q&A at the end of each lecture. Walker addressed students’ concerns about the U.S. response to the pandemic, the risk of reinfection, mutability of the virus, and challenges with new types of vaccines. With the aim of providing accurate information, his answers were not always reassuring. However, in spite of the many uncertainties that the scientists are grappling with, the course faculty’s message for students is an optimistic one.

“People have felt powerless in this pandemic,” Afeyan says. “A course like this can help people feel like they have the tools to do something about it. There is a plethora of problems that will stem from the pandemic, so there are lots of ways to get involved regardless of your field.”

Researchers have banded together across MIT, Whitehead Institute, Ragon Institute, and around the globe to address the pandemic. For students who want to join the research effort, the content of the lectures is paired with discussions during Afeyan’s sessions with researchers earlier in their careers, who can talk to the students about next steps should they choose to pursue one of the fields presented in the course.

As for students and audience members simply looking to understand the public health event that has so strongly impacted their world, the faculty hope that the course will provide them with the answers they need. Scientists are not the only ones dealing with lots of uncertainty these days, and there is value in learning what the experts know as they know it, straight from the source.

Defining a “new normal” for campus research

Despite the trials and tribulations of the COVID-19 pandemic, Building 68 core facilities have remained open for business.

Raleigh McElvery
September 10, 2020

In mid-March, MIT closed its doors due to the COVID-19 pandemic, and Building 68 temporarily became a ghost town. Home to over 25 life science labs and three core facilities, the Department of Biology’s primary research hub usually teems with activity. But this spring, only a skeleton crew of essential workers came in and out, maintaining the equipment and running select experiments. Since then, the ghost town has gradually come back to life, as scientists are returning to their benches once again while taking safety precautions.

Three of the 24 core facilities affiliated with the life sciences are located in Building 68: the BioMicro Center, Structural Biology Core Facility, and Biophysical Instrumentation Facility. Known fondly as the “BIF,” the latter houses instruments that help researchers elucidate macromolecular structures. Select staff members remained available throughout the research shutdown to help biologists, biological engineers, and chemists run essential protocols.

One floor down, the BioMicro Center also continued to offer limited services — from maintaining multi-year cancer studies to running analyses probing SARS-CoV-2, the virus strain that causes COVID-19. The team there specializes in genomic and transcriptomic technologies, bioinformatics, and research computing.

Stuart Levine SB ’97,  who leads the BioMicro Center, says the facility handled anywhere from six to nine projects a day before the pandemic. But during the research shutdown, requests dwindled to a steady “trickle.”

“We did whatever we could to be helpful,” he adds. “I went to campus a few times early on, and it was eerie to be one of the only people in the building.”

Illustration of virus-like molecule
Illustration of the Bathe lab’s virus-like nanoparticle. Credit: Ella Maru Design Studio

Although the BioMicro Center is situated in Building 68, it serves a wide array of individuals and labs across campus. Chemical engineering graduate student, Grant Knappe, was also among the select few permitted to work in lab during the shutdown, and he relied heavily on the BioMicro Center for a key step in his experimental protocol. Knappe’s advisor, Professor of Biological Engineering Mark Bathe, began shifting his group’s focus to COVID-related projects almost immediately after campus emptied in mid-March.

The Bathe lab studies nanoparticles made from DNA “origami” that’s been folded into tiny geometric shapes. They’ve developed user-friendly algorithms to design these structures, and regularly employ the BioMicro’s oligonucleotide synthesizer to produce their DNA strands. With the help of the facility, Knappe and his colleagues recently created nanoparticles adorned with short DNA strands to mimic the SARS-CoV-2 spike protein — which induces the body’s immune response. They hope these geometric nanoparticles will eventually help develop COVID-19 vaccines.

“The scientific process is usually very collaborative,” Knappe says, “so at the beginning it was difficult to run experiments without other people nearby to bounce ideas back-and-forth.”

Focusing on just one project — rather than several simultaneously — was also a new experience. Knappe is excited to see where his COVID research will go, and what lab instruments will ultimately be key to the process. “You never know what equipment could end up fighting the virus,” he adds.

On June 1, Phase 1 of the research ramp-up began, and labs were permitted to begin operating at 25% capacity. Scientists started working in shifts with reduced hours, conducting their experiments many feet apart, and visiting MIT Medical for regular COVID-19 testing. Levine remembers that the number of requests for BioMicro services surged almost immediately as researchers returned.

At the same time, Robert Grant, the Research Scientist responsible for the Structural Biology Core Facility, started up the core’s state-of-the-art X-ray crystallography equipment. Leaving in March had been a “mad scramble,” and he remembers hastily terminating non-essential experiments and distributing extra resources (like liquid nitrogen tanks) to labs in-need. When he returned in June he already had project requests.

“A big part of my job is interacting with people, which I really enjoy,” he says. “But we’ve had to adapt, and and devise new ways to train people on equipment and data processing that don’t require close contact.”

Grant has recently started socially distant one-on-one trainings, where both parties remain as far apart as possible while wearing masks and gloves. In some cases, he’s processed samples and collected data for users, helping them perform analyses via Zoom. He’s also found ways to revive collaborations with other institutes. He recently sent crystals to Argonne National Laboratory in Chicago. The student who grew the crystals then remotely controlled an X-ray beamline at Argonne’s Advanced Photon Source synchrotron to collect diffraction data from home while Zooming with Grant.

“We’re definitely open for business, although things look a little different than before,” Grant says. “We’ve reached a new normal.”

Building 68's Structural Biology Core Facility
Building 68’s Structural Biology Core Facility
Posted: 9.10.20
School of Science grows by 10
School of Science
September 9, 2020

Despite the upheaval caused by the coronavirus pandemic, 10 new faculty members have joined MIT in the departments of Biology; Chemistry; Earth, Atmospheric and Planetary Sciences; Mathematics; and Physics. The School of Science welcomes these new faculty, most of whom began their appointment July 1, amidst efforts to update education and research plans for the fall semester. They bring exciting and valuable new areas of strength and expertise to the Institute.

Camilla Cattania is an earthquake scientist. She uses continuum mechanics, numerical simulations, and statistics to study fault mechanics and earthquake physics at different scales, from small repeating events to fault interaction on regional and global scales. The models she has developed can help forecast earthquake sequences caused by seismic or aseismic events, such as aftershocks and swarms induced by forcing mechanisms like magma moving under the Earth’s surface. She has also developed theoretical models to explain why certain faults rupture in predictable patterns while others do not. Cattania’s research plans include widening her focus to other tectonic settings and geometrically complex fault structures.

Cattania earned her bachelor’s and master’s degrees from Cambridge University in experimental and theoretical physics in 2011, after which she completed a PhD in Germany at the GFZ German Research Center for Geosciences and the University of Potsdam in 2015. Subsequently, she spent a few months as a researcher at Woods Hole Oceanographic Institution and as a postdoc at Stanford University and her doctoral institution. She joins the Department of Earth, Atmospheric and Planetary Sciences as an assistant professor.

Richard Fletcher researches quantum physics using atomic vapors one-millionth the density of air and one-millionth the temperature of deep space. By manipulating the gas with intricately sculpted laser beams and magnetic fields, he can engineer custom-made quantum worlds, which provide both a powerful test bed for theory and a wonderful playground for discovering new phenomena. The goal is to understand how interesting collective behaviors emerge from the underlying microscopic complexity of many interacting particles. Fletcher’s interests include superfluidity in two-dimensional gases, methods to probe the correlations between individual atoms, and how the interplay of interactions and magnetic fields leads to novel physics.

Fletcher is a graduate of Cambridge University, where he completed his bachelor’s in 2010. Before returning to Cambridge University to earn his PhD in 2015, he was a research fellow at Harvard University. He originally came to MIT as a postdoc in 2016 and now joins the Department of Physics as an assistant professor. Fletcher is a member of the MIT-Harvard Center for Ultracold Atoms.

William Frank investigates deformation of the Earth’s crust. He combines seismology and geodesy to explore the physical mechanisms that control the broad continuum of rupture modes and fault instabilities within the Earth. His research has illuminated the cascading rupture dynamics of slow fault slip and how the aftershocks that follow a large earthquake can reveal the underlying behavior of the host fault. Frank considers shallow shifts that cause earthquakes down to deep creep that is all-but-invisible at the surface. His insights work to improve estimates of seismic hazards induced by tectonic dynamics, volcanic processes, and human activity, which can then inform risk prediction and mitigation.

Frank holds a bachelor’s degree from the University of Michigan in earth systems science, which he received in 2009. The Institut de Physique du Globe de Paris awarded him a master’s degree in geophysics in 2011 and a PhD in 2014. He first joined MIT as a postdoc in 2015 before moving to the University of Southern California as an assistant professor in 2018. He now returns as an assistant professor in the Department of Earth, Atmospheric and Planetary Sciences.

Ronald Fernando Garcia Ruiz advances research on fundamental physics and nuclear structure largely through the development of novel laser spectroscopy techniques. He investigates the properties of subatomic particles using atoms and molecules made up of short-lived radioactive nuclei. Garcia Ruiz’s experimental work provides unique information about the fundamental forces of nature and offers new opportunities in the search beyond the Standard Model of particle physics. His previous research at CERN focused on the study of the emergence of nuclear phenomena and the properties of nuclear matter at the limits of existence.

Garcia Ruiz’s bachelor’s degree in physics was achieved in 2009 at Universidad Nacional de Colombia. After earning a master’s in physics in 2011 at Universidad Nacional Autónoma de México, he completed a doctoral degree in radiation and nuclear physics at KU Leuven in 2015. Prior to joining MIT, he was first a research associate at the University of Manchester from 2016-17 and then a research fellow at CERN. Garcia Ruiz has now joined the Department of Physics as an assistant professor. He began his appointment Jan. 1. He is also affiliated with the Laboratory for Nuclear Science.

Ruth Lehmann studies germ cells. The only cells in the body capable of producing an entire organism on their own, germ cells pass genomic information from one generation to the next via egg cells. By analyzing the organization of their informational material as well as the mechanics they regulate, such as the production of eggs and sperm, Lehmann hopes to expose germ cells’ unique ability to enable procreation. Her work in cellular and developmental biology is renowned for identifying how germ cells migrate and lead to the continuation of life. An advocate for fundamental research in science, Lehmann studies fruit flies as a model to unveil vital aspects of early embryonic development that have important implications for stem cell research, lipid biology, and DNA repair.

Lehmann earned her bachelor’s degree in biology from the University of Tubingen in Germany. She took an interlude from her education to carry out research at the University of Washington in the United States before returning to Germany. There, she earned a master’s equivalent from the University of Freiburg and a PhD from the University of Tubingen. Lehmann was subsequently a postdoc at the Medical Research Council Laboratory of Molecular Biology in the UK, after which she joined MIT. A faculty member and Whitehead Institute for Biomedical Research member from 1988 to 1996, she now returns after 23 years at New York University. Lehmann joins as a full professor in the Department of Biology and is the new director of the Whitehead Institute for Biomedical Research.

As an astrochemist, Brett McGuire is interested in the chemical origins of life and its evolution. He combines physical chemistry experiments and analyses with molecular spectroscopy in a lab, the results of which he then compares against astrophysics observation. His work ties together questions about the formation of planets and a planet’s ability to host and create life. McGuire does this by investigating the generation, presence, and fate of new molecules in space, which is vast and mostly empty, providing unique physical challenges on top of chemical specifications that can impact molecular formation. He has discovered several complex molecules already, including benzonitrile, a marker of carbon-based reactions occurring in an interstellar medium.

McGuire’s BS degree was awarded by the University of Illinois at Urbana-Champaign in 2009. He completed a master’s in physical chemistry in 2011 at Emory University and a PhD in 2015 at Caltech. He then pursued a postdoc at the National Radio Astronomy Observatory and the Harvard-Smithsonian Center for Astrophysics. He joins the Department of Chemistry as an assistant professor.

Dor Minzer works in the fields of mathematics and theoretical computer science. His interests revolve around computational complexity theory, or — more explicitly — probabilistically checkable proofs, Boolean function analysis, and combinatorics. With collaborators, he has proved the 2-to-2 Games Conjecture, a central problem in complexity theory closely related to the Unique-Games Conjecture. This work significantly advances our understanding of approximation problems and, in particular, our ability to draw the border between computationally feasible and infeasible approximation problems.

Minzer is not new to online education. After earning his bachelor’s degree in mathematics in 2014 and a PhD in 2018, both from Tel-Aviv University, he became a postdoc at the Institute for Advanced Study at Princeton University. He joins the Department of Mathematics as an assistant professor.

Lisa Piccirillo is a mathematician specializing in the study of three- and four-dimensional spaces. Her work in four-manifold topology has surprising applications to the study of mathematical knots. Perhaps most notably, Piccirillo proved that the Conway knot is not “slice.” For all other small knots, “sliceness” is readily determined, but this particular knot had remained a mystery since John Conway presented it in the mid-1900s. After hearing about the problem at a conference, Piccirillo took only a week to formulate a proof. She is broadly interested in low-dimensional topology and knot theory, and employs constructive techniques in four-manifolds.

Piccirillo earned her BS in mathematics in 2013 from Boston College. Her PhD in mathematics was earned from the University of Texas at Austin in 2019, and from 2019-20 she was a postdoc at Brandeis University. She joins the Department of Mathematics as an assistant professor.

Jonathan Weissman’s research interest is protein folding and structure, an integral function of life. His purview encompasses the expression of human genes and the lineage of cells, as well as protein misfolding, which can cause diseases and other physiological issues. He has made discoveries surrounding protein folding mechanisms, the development of CRISPR gene-editing tools, and other new therapeutics and drugs, and in the process generated innovative experimental and analytical methods and technologies. One of his novel methods is the ribosome profiling approach, which allows researchers to observe in vivo molecular translation, the process by which a protein is created according to code provided by RNA, a major advancement for health care.

Weissman earned a bachelor’s degree in physics from Harvard University in 1998 and a PhD from MIT in 1993. After completing his doctoral degree, he left MIT to become a postdoc at Yale University for three years, and then a faculty member at the University of California at San Francisco in 1996. He returns to MIT to join the Department of Biology as a full professor and a member of the Whitehead Institute for Biomedical Research. He is also a Howard Hughes Medical Institute investigator.

Yukiko Yamashita, a stem cell biologist, delves into the origins of multicellular organisms, asking questions about how genetic information is passed from one generation to the next, essentially in perpetuity, via germ cells (eggs and sperm), and how a single cell (fertilized egg) becomes an organism containing many different types of cells. The results of her work on stem cell division and gene transmission has implications for medicine and long-term human health. Using fruit flies as a model in the lab, she has revealed new areas of knowledge. For example, Yamashita has identified the mechanisms that enable a stem cell to produce two daughter cells with distinct fates, one a stem cell and one a differentiating cell, as well as the functions of satellite DNA, which she found to be crucial, unlike the “waste” they were previously thought to be.

Yamashita received her bachelor’s degree in biology in 1994 and her PhD in biophysics in 1999, both from Kyoto University. After being a postdoc at Stanford University for five years, she was appointed a faculty member at the University of Michigan in 2007. She joined the Department of Biology as a full professor with a July 1 start. She also became a member of the Whitehead Institute of Biomedical Research and is a standing investigator at the Howard Hughes Medical Institute.

Sebastian Lourido earns ASM Award for Early Career Basic Research
August 28, 2020

Washington, D.C. – August 27, 2020 – The 2021 American Society for Microbiology (ASM) awardees in research, education and leadership have now been announced. ASM congratulates all of the award recipients for their achievements. The ASM Awards program is managed by the American Academy of Microbiology, the honorific leadership group within ASM. The mission of the Academy is to recognize microbiologists for outstanding contributions to the microbial sciences and to provide microbiological expertise in the service of science and the public.

The 2021 ASM Award Laureates:

ASM Alice C. Evans Award for Advancement of Women
Recognizes outstanding contributions toward the full participation and advancement of women in the microbial sciences. This award is given in memory of Alice C. Evans, the first woman to be elected ASM president (elected in 1928).
•    Jennifer Glass, Ph.D.

ASM Award for Applied and Biotechnological Research
Recognizes an outstanding scientist with distinguished research achievements in the development of products, processes and technologies that have advanced the microbial sciences.
•    Dennis Hruby, Ph.D.

ASM Award for Early Career Applied and Biotechnological Research
Recognizes an early career investigator with distinguished research achievements in the development of products, processes and technologies that have advanced the microbial sciences.
•    Kizzmekia Corbett, Ph.D.

ASM Award for Basic Research
Recognizes an outstanding scientist whose discoveries have been fundamental to advancing our understanding of the microbial world.
•    Sue Wickner, Ph.D.

ASM Award for Early Career Basic Research
Recognizes an early career investigator with distinguished basic research achievements in the microbial sciences.
•    Sebastian Lourido, Ph.D.

ASM Award for Environmental Research
Recognizes an outstanding scientist with distinguished research achievements that have improved our understanding of microbes in the environment, including aquatic, terrestrial and atmospheric settings.
•    Terry Hazen, Ph.D.

ASM Award for Early Career Environmental Research
Recognizes an early career investigator with distinguished research achievements that have improved our understanding of microbes in the environment, including aquatic, terrestrial and atmospheric settings.
•    A. Murat Eren, Ph.D.

ASM Award for Education
Recognizes general excellence in microbiology education. Education is broadly defined and meant to include any and all activities that inform and motivate students about the discipline of microbiology.
•    Nichole Broderick, Ph.D.

ASM Award for Research and Leadership in Clinical Microbiology
Recognizes an outstanding scientist/clinical microbiologist with distinguished research achievements, and a record of innovation and advancement of the clinical microbiology profession. This award represents the merging of the BD Research and Sonnenwirth Awards given annually since 1978 and 1986, respectively.
•    Melissa Miller, Ph.D.

ASM Award for Service
Recognizes outstanding contributions through service to the microbiological community.
•    Barbara Robinson-Dunn, Ph.D.

ASM Carski Award
Recognizes an educator for outstanding teaching of microbiology to undergraduate students and for encouraging them to subsequent achievement.
•    Jason Tor, Ph.D.

ASM D.C. White Award
Recognizes distinguished accomplishments in interdisciplinary research and mentoring in microbiology. This award honors D.C. White, who was known for his interdisciplinary scientific approach and for being a dedicated and inspiring mentor.
•    Ferran Garcia-Pichel, Ph.D.

ASM Lifetime Achievement Award
ASM’s premier award for sustained contributions to the microbiological sciences.
•    Bernard Moss, MD, Ph.D.

ASM Moselio Schaechter Award in Recognition of a Developing-Country Microbiologist
This award, named in honor of Professor Moselio Schaechter, former ASM president, recognizes a scientist who has shown exemplary leadership and commitment towards the substantial furthering of the profession of microbiology in research, education or technology in the developing world.
•    Gustavo Goldman, Ph.D.

ASM Scherago-Rubin Award for Clinical Microbiology
Recognizes an outstanding bench-level clinical microbiologist involved in routine diagnostic work that has distinguished her- or himself by excellent performance. The award was established by the late Sally Jo Rubin, an active member of ASM’s Clinical Microbiology Division, in honor of her grandfather, Professor Morris Scherago.
•    Brandon Ellis, B.S.

ASM William A. Hinton Award for Advancement of a Diverse Community of Microbiologists
Recognizes outstanding contributions toward fostering the research training of minorities and in increasing diversity in microbiology. It is given in memory of William A. Hinton, a physician-research scientist, and one of the first African-Americans to join ASM.
•    Eric Triplett, Ph.D.

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The American Society for Microbiology is one of the largest professional societies dedicated to the life sciences and is composed of 30,000 scientists and health practitioners. ASM’s mission is to promote and advance the microbial sciences.

ASM advances the microbial sciences through conferences, publications, certifications and educational opportunities. It enhances laboratory capacity around the globe through training and resources. It provides a network for scientists in academia, industry and clinical settings. Additionally, ASM promotes a deeper understanding of the microbial sciences to diverse audiences.

“Runaway” Transcription

Researchers discover new rules governing bacterial gene expression that overturn fundamental assumptions about basic biological pathways.

Raleigh McElvery
August 26, 2020

On the evolutionary tree, humans diverged from yeast roughly one billion years ago. By comparison, two seemingly similar species of bacteria, Escherichia coli and Bacillus subtilis, have been evolving apart for roughly twice as long. In other words: walking, talking bipeds are closer on the tree of life to single-celled fungus than these two bacteria are to one another. In fact, it’s becoming increasingly clear that what is true of one bacterial type may not be true of another — even when it comes down to life’s most basic biological pathways.

E. coli has served as a model organism in scientific research for over a century, and helped researchers parse many fundamental processes, including gene expression. In these bacteria, as one molecular machine, the RNA polymerase, moves along the DNA transcribing it into RNA, it is followed in close pursuit by a second molecular machine, the ribosome, which translates the RNA into proteins. This “coupled” transcription-translation helps monitor and tune RNA output, and is considered a hallmark of bacteria.

However, an interdisciplinary team of biologists and physicists recently showed that the B. subtilis bacterium employs a different set of rules. Rather than working in tandem with the ribosome, the polymerase in B. subtilis speeds ahead. This system of “runaway” transcription creates alternative rules for RNA quality control, and provides insights into the sheer diversity of bacterial species.

“Generations of researchers, including myself, were taught that coupled transcription-translation is fundamental to bacterial gene expression,” says Gene-Wei Li, an associate professor of biology and senior author of the study. “But our very precise, quantitative measurements have overturned that long-held view, and this study could be just the tip of the iceberg.”

Grace Johnson, a graduate student in the Department of Biology, and Jean-Benoît Lalanne, a graduate student in the Department of Physics, are the lead authors on the paper, which appeared in Nature on Aug. 26.

A curious clue

In 2018, Lalanne developed an experimental technique to measure the boundaries of RNA transcripts. When DNA is transcribed into RNA, the resulting transcripts are generally longer than the DNA coding sequence because they also have to include an extra bit at the end to signal the polymerase to stop. In B. subtilis, Lalanne noticed there simply wasn’t enough space between the ends of the coding sequences and the ends of the RNA transcripts — the extra code was too short for both the polymerase and the ribosome to fit at the same time. In this bacterium, coupled transcription-translation didn’t seem possible.

“It was a pretty weird observation,” Lalanne recalls. “It just didn’t square up with the accepted dogma.”

To delve further into these puzzling observations, Johnson measured the speeds of the RNA polymerase and ribosome in B. subtilis. She was surprised to find that they were moving at very different rates: the polymerase was going roughly twice as fast as the ribosome.

During coupled transcription-translation in E. coli, the ribosome is so closely associated with the RNA polymerase that it can control when transcription terminates. If the RNA encodes a “premature” signal for the polymerase to stop transcribing, the nearby ribosome can mask it and spur the polymerase on. However, if something goes awry and the ribosome is halted too far behind the polymerase, a protein called Rho can intervene to terminate transcription at these premature sites, halting the production of these presumably non-functional transcripts.

However, in B. subtilis, the ribosome is always too far behind the polymerase to exert its masking effect. Instead, Johnson found that Rho recognizes signals encoded in the RNA itself. This allows Rho to prevent production of select RNAs while ensuring it doesn’t suppress all RNAs. However, these specific signals also mean Rho likely has a more limited role in B. subtilis than it does in E. coli.

A family trait

To gauge how common runaway transcription is, Lalanne created algorithms that sifted through genomes from over 1,000 bacterial species to identify the ends of transcripts. In many cases, there was not enough space at the end of the transcripts for both the RNA polymerase and the ribosome to fit, indicating that more than 200 additional bacteria also rely on runaway transcription.

“It was striking to see just how widespread this phenomenon is,” Li says. “It raises the question: How much do we really know about these model organisms we’ve been studying for so many years?”

Carol Gross, a professor in the Department of Microbiology and Immunology at University of California San Francisco who was not involved with the study, refers to the work as a “tour de force.”

“Gene-Wei Li and colleagues show transcription-translation coupling, thought to be a foundational feature of bacterial gene regulation, is not universal,” she says. “Instead, runaway transcription leads to a host of alternative regulatory strategies, thereby opening a new frontier in our study of bacterial strategies to thrive in varied environments.”

As researchers widen their experimental radius to include more types of bacteria, they are learning more about the basic biological processes underlying these microorganisms — with implications for those that take up residence in the human body, from helpful gut microbes to noxious pathogens.

“We’re beginning to realize that bacteria can have distinct ways of regulating gene expression and responding to environmental stress,” Johnson says. “It just shows how much interesting biology is left to uncover as we study increasingly diverse bacteria.”

Citation:
“Functionally uncoupled transcription–translation in Bacillus subtilis”
Nature, online August 26, 2020, DOI: 10.1038/s41586-020-2638-5
Grace E. Johnson, Jean-Benoît Lalanne, Michelle L. Peters, and Gene-Wei Li

Top illustration: Researchers discovered a new system of transcription and translation in bacteria, where the polymerase (pink) in B. subtilis “runs away” from the ribosome (blue). Credit: Grace Johnson
Posted: 8.26.20
Antibiotic resistance: How to prevent the next public health emergency
Emma H. Yee, Steven S. Cheng, Grant A. Knappe, and Christine A. Moomau | MIT Science Policy Review
August 25, 2020

Article Summary

Antibiotics are a vital component of global health. By killing or inhibiting the growth of bacteria, antibiotics treat infections like pneumonia, staph, and tuberculosis.By preventing infections, they enable major medical procedures such as surgeries and chemotherapy. However,bacteria are becoming increasingly resistant to current antibiotics, causing an estimated 34,000 deaths annually in the US. Left unchecked, antibiotic resistance will have major public health consequences, causing over 5 million deaths each year by 2050. Major causes of this crisis are the misuse of existing antibiotics and the slow development of new antibiotics. To incentivize responsible use, governments and institutions are initiating education programs, mandating comprehensive hospital antibiotic stewardship programs, and funding the development of rapid diagnostics. To bring new antibiotic drugs to market, the US government and other non-governmental organizations are funding scientific research toward antibiotic development.Additional incentives are being pursued to improve the commercial viability of antibiotic development and protect drug developers from the unique challenges of the antibiotic market. With diligent efforts to improve responsible use and encourage novel antibiotic drug discovery, we can decrease the global disease burden, save money, and save lives.

Antibiotics are drugs that kill or inhibit the growth of bacteria, and we have them to thank for the 25-year increase in American life expectancy in the last century[1,2]. In 1900, the three leading causes of death were bacterial infections: pneumonia, tuberculosis, and diarrhea/enteritis[3]. Penicillin, the first antibiotic, was discovered in 1928. But it was not until World War II, when wounded soldiers were more likely to die from infections than the injuries themselves, that governments realized penicillin’s life-saving potential[4]. The US government began developing and mass-producing penicillin through unprecedented public, private, and international collaborations, prompting a new era of antibiotics. Antibiotics are now used to treat a myriad of common infections like strep throat, meningitis, tuberculosis, tetanus, urinary tract infections, and food poisoning. They also enable medical procedures that otherwise create a high risk of infection, such as invasive surgery, organ transplantation, and chemotherapy[5]. However, antibiotics are not “one size fits all”; certain types of antibiotics are only effective against certain kinds of bacteria, and all antibiotics are ineffective against viruses[6].

Antibiotics kill or inhibit bacterial growth via various mechanisms of action; they might attack the protective bacterial cell wall, interfere with bacterial reproduction, or interrupt production of molecules necessary for the bacteria’s survival[7]. However, bacteria reproduce and evolve rapidly, changing over time to resist an antibiotic’s destructive mechanism of action. In fact, the more we use antibiotics, the faster bacteria evolve to resist those antibiotics. As bacteria reproduce, random DNA mutations will occur. Most random mutations have no effect on the bacteria, but sometimes a mutation will give the bacteria a special ability to resist an antibiotic—for instance, the mutation may change the cellular target of the antibiotic, or allow the bacteria to pump the drug out of the cell. When an antibiotic is used on bacteria, most of the population will die, but if any of the bacteria have one of these resistance-conferring mutations, they will survive and continue to reproduce, until the entire population is resistant[5]. The use of antibiotics therefore creates environments where bacteria with antibiotic resistance mutations are more likely to survive and reproduce, while susceptible bacteria are gradually killed off.

Figure 1: Use of an antibiotic gradually increases the prevalence of resistant bacteria. If any cell has developed characteristics allowing it to resist attack by an antibiotic, it is more likely to survive and multiply.

This means that, over time, the bacteria that cause infections in humans are more and more likely to be resistant to common antibiotics. It is important to note that bacteria develop antibiotic resistance–not people. But when people use lots of antibiotics, they change bacterial populations such that more and more bacteria are resistant to those antibiotic drugs. This illustrates the double-edged sword nature of antibiotic use: antibiotics are immensely valuable for combating countless infections and enabling medical procedures, but the more we use them, the less valuable they become.

Today, antibiotic resistance is accelerating at alarming rates. The Centers for Disease Control and Prevention (CDC) estimates there are 3 million antibiotic resistant infections in the US every year, causing at least 34,000 deaths[5]. Globally, at least 700,000 deaths occur due to resistant infections, most of which are bacterial; the actual number is likely higher due to poor reporting and surveillance[8]. The prospect of widespread antibiotic resistance threatens to bring society into a post-antibiotic age where infections are more expensive and difficult to treat. This is a threat to not only public health but also the economic stability of the healthcare system[9] and national security[10].

Figure 2:Annual global deaths due to different factors. Antimicrobial resistance (AMR) accounts for resistance from bacteria, as well as fungi, viruses, parasites, and other microbes[15].
This review will focus on medical use of antibiotics in humans in the US, but antibiotic use in animals and agriculture are also major contributors to the current crisis[6]. It is also critical to understand that combating antibiotic resistance will require global cooperative action because infection-causing bacteria spread rapidly between cities, countries, and continents. A large part of addressing antibiotic resistance in the US is assisting and coordinating with other governments, especially those in low-income countries which have the highest instances of antibiotic resistance, but the fewest resources to deal with it[11]. It is also vital to understand the causes of antibiotic resistance in the US and effective actions US institutions can take.

Misuse and Overuse of Antibiotics

Overuse of antibiotics is a major contributor to the rapid proliferation of antibiotic resistant infections. It is estimated that US doctors’ offices and emergency departments prescribe about 47 million unnecessary antibiotic courses annually, amounting to 30% of all antibiotic prescriptions[12]. Many studies show that even when illnesses do require antibiotics, prescribed time courses are significantly longer than national guidelines[13, 14].

Rapid Diagnostics and Antibiotic Prescriptions: A major cause of ubiquitous antibiotic overuse is a lack of rapid methods for diagnosing infections. Physicians rely on tests that usually take days to weeks to identify if an infection is bacterial and, if so, which antibiotics will be most effective. Waiting this long can be harmful or even fatal for patients[15]. Therefore, physicians usually prescribe broadly effective antibiotics while knowing little about the nature of the infection[15]. This can save lives, but if the infection is caused by a virus or resistant bacteria, the antibiotics will not treat the illness and will give resistant strains a chance to further multiply, leaving patients susceptible to additional infections.

With growing awareness in the last 5-10 years that appropriate antibiotic use is difficult with current diagnostics, the CDC, the National Institute of Allergy and Infectious Diseases (NIAID), and the Biomedical Advanced Research and Development Authority (BARDA) have collectively awarded hundreds of millions of dollars to state health departments, businesses, and universities to develop rapid diagnostics[16]. BARDA and NIAID also organized a $20 million prize, the Antimicrobial Resistance Diagnostic Challenge[17], and fund the global non-profit, CARB-X, which has invested $82.5 million in 55 projects worldwide for antibiotic resistance research, including diagnostics[18]. This surge in resources and funding has increased rapid diagnostic development. For example, the NIAID funded development of BioFire’s FilmArray[19], which is now an FDA-cleared diagnostic test available for purchase in the US[20]. In just an hour, it tests patient samples for several common types of bacteria, viruses, and yeast, including antibiotic resistant ones[21].

However, new diagnostic technologies have limited effectiveness when they fail to meet practical cost and resource requirements. Cepheid’s GeneXpert MTB/RIF test, for example, can diagnose tuberculosis infection and determine resistance to rifampicin, a common antibiotic for tuberculosis, in 2 hours[22]. Unfortunately, it has not been used as widely as initially expected[23], mainly because the equipment costs $17,000, not counting training and set-up costs[24]. This illustrates another major shortcoming of current diagnostic technologies: high healthcare infrastructure and cost requirements that render them inaccessible to many people.

Widespread access to rapid diagnostics is not just about fairness, it’s a necessity. Antibiotic resistance will remain a problem in the US as long as it is a problem anywhere in the country or the world due to inevitable intra- and international bacterial transmission. Many recently developed rapid diagnostics cost $100-$250 per test[25, 26]. These diagnostic innovations are promising and valuable in filling part of the gap in rapid diagnostics, but their benefits will not be felt by the majority of global hospitals and patients that cannot afford or support high cost, high tech diagnostic investments. Increasing institutional funding in the last 10 years has resulted in new rapid diagnostics for identifying and characterizing infections, a potential step towards reducing antibiotic misuse and subsequent development of antibiotic resistance. However, ensuring accessibility of technological improvements is essential in combating antibiotic resistance.

Prescribing Practices: Updating prescription standards and educating healthcare workers and patients on responsible antibiotic use is another key step in reducing antibiotic overuse. In the US, patients are often prescribed antibiotics for far longer than necessary. Two recent studies found that 70% of patients with sinus infections and 70% of adults hospitalized with pneumonia were given antibiotics for 3 or more days longer than recommended[13, 14]. Oftentimes, this stems from an out-of-date belief that longer is better in terms of preventing the development and spread of resistant bacteria. In fact, the opposite is true. Shorter courses of antibiotics lower the selective pressure for development of resistance. This was illustrated in a study of pediatric antibiotic use[27], where children prescribed 5 days of amoxicillin for the treatment of respiratory infections were less likely to carry antibiotic resistant Streptococcus pneumoniae in their nasal passage than their peers who were treated for 10 days. These children were also found to be less likely to transmit resistant bacteria to others.

In many cases, common antibiotic treatments can be shortened without affecting the outcome. A trial of pneumonia patients found that the standard 8-day course of amoxicillin can be shortened to just 3 days with equal symptom relief and fewer side effects[28]. Similarly, treatment of ventilator-associated pneumonia can be effectively shortened from 14 to 8 days[29]. In some cases, shortened antibiotic courses have actually improved patient outcomes. A reduced course for urinary tract infections from 14 days to 7 days is not only effective, it also prevents post-treatment yeast infections[30].

As scientists and clinicians become more aware of the dangers of resistance, more studies are being conducted to determine the minimum amount of antibiotic required to adequately treat infections. The Infectious Diseases Society of America has also updated their Clinical Practice Guidelines to reflect findings that shorter treatment schedules are often just as effective, are easier to comply with, and reduce development and spread of resistant bacteria[31]. Performing
minimum effective antibiotic treatment trials is costly in the short term, but necessary to safely revise guidelines and save on long-term healthcare costs.

Public misunderstanding and misinformation regarding antibiotics also contribute to their overprescription. In many clinical settings where antibiotics are not necessary, patients may believe antibiotics are the most effective treatment and push their doctors to inappropriately prescribe them. For example, patients often seek antibiotics for viral respiratory illnesses (i.e. cold and flu), despite antibiotics being ineffective against viral infections[5]. It has been demonstrated that patient expectation of antibiotics or physician perception of this desire have a significant influence on antibiotic prescription[32–34].

Table 1: Antibiotic overuse is caused largely by shortcomings in diagnostic technologies and prescribing practices, but there are many possible ways to address these challenges.

Efforts to address this issue include educational initiatives for the public and antibiotic stewardship programs for healthcare providers. One such initiative was France’s national campaign to reduce antibiotic use, launched in 2001[35]. France, Europe’s largest antibiotics consumer, sought to address the problem through physician training and a public health campaign called “Antibiotics are not automatic”. This campaign spread public awareness that overusing antibiotics leads to resistance, and, during the winter flu season, that antibiotics kill bacteria – not the viruses responsible for most respiratory infections. Concurrently with this initiative, antibiotic use in France dropped by over 25% from 2000 to 2007, highlighting the ability of public health education to change clinical outcomes. In recent years, steps have been taken both in the US and internationally to encourage responsible antibiotic use via education, updated prescribing standards, and other courses of action. In 2016, the Joint Commission on Hospital Accreditation, an organization that accredits US healthcare organizations, mandated antibiotic stewardship programs in US hospitals that participate in Medicare and Medicaid. The Joint Commission issued standards cited from the CDC’s Core Elements of Hospital Antibiotic Stewardship Programs[36], including educating staff, healthcare practitioners, patients, and their families on responsible antibiotic use and resistance, appointing a pharmacist leaders to improve hospitals’ antibiotic use, tracking and reporting antibiotic prescribing and resistance patterns, and developing protocols for specific antibiotic use cases, such as pneumonia. The number of hospitals reporting an antibiotic stewardship program that meets all the CDC’s Core Elements doubled between 2014 and 2017[37], and will likely increase further, with stewardship programs now tied to accreditation. On an international scale, the UN and CDC have pushed for global implementation of One Health responses by releasing recommendations for engaging all members of society—governments, businesses, healthcare workers, etc.—in coordinated and strategic efforts to address antibiotic resistance[8]. Comprehensive promotion of responsible antibiotic use is vital to maintaining their usefulness for as long as possible, especially given the difficulty of developing new antibiotics.

Revitalizing the Antibiotic Pipeline

While it is important that existing antibiotics are prescribed cautiously and used responsibly, all antibiotics inevitably encounter resistance[38]. Consequently, continuously developing antibiotics with novel mechanisms of action—the method that an antibiotic uses to kill bacteria—that circumvent existing resistances will remain essential. However, developing these new drugs is costly; it can take well over a decade and cost more than $2 billion, with a 90% failure rate looming over the project[38]. Clinical trials, which require large, diverse populations to demonstrate evidence of drug superiority, account for 65% of the risk-adjusted cost for developing antibiotics[15]. The difficulty of antibiotic drug development is illustrated by the 2019 FDA approval of lefamulin, which marked the first approval of an IV/orally-administered antibiotic with a novel mechanism of action in two decades[39]. Scientific challenges inhibit discovery significantly. The immediately apparent antibiotic candidates have been developed, and discovering antibiotics with new mechanisms of action is challenging. It is now thought that any new, effective antibiotics will need multiple capabilities for killing bacteria, making their discovery more complex[3]. Emerging approaches in antibiotic discovery such as deep learning algorithms are promising technologies to solve these scientific challenges, but are far from bringing new antibiotics to patients[40].

In addition to scientific obstacles, the economics of antibiotic development have reduced innovation and output. The free market is failing to meet society’s antibiotic needs via multiple pathways[41]. Traditional sales-based models, in which revenue is directly proportional to the volume of sales, are antagonistic towards society’s goal of sustainable antibiotic use[2]. Evidence of the current system’s failure is the drastic decrease in antibiotic research programs[3] and the sparse output of new [2]. To address these challenges, policymakers are crucial actors; they can facilitate fertile economic conditions using a combination of 1) “push” policies to galvanize antibiotic discovery and development efforts and 2) “pull” policies to create profitable
economic conditions, incentivizing industry to work in this area. Simultaneously, these policies must be supplemented by sufficient regulations to ensure sustainable and equitable usage, broadly maximizing overall societal benefits.

Push Policies: Push policies drive companies to conduct antibiotic research and clinical trials[42] by providing monetary resources to antibiotic developers. Push policies are realized via grants and pipeline coordinators. Government grants allow both academia and industry to investigate antibiotic candidates and conduct clinical trials. Pipeline coordinators are agencies that ensure governmental funding is distributed efficiently across development stages. Coordinators are essential to ensuring equitable funding distribution across antibiotic candidates and identifying gaps and needs in the antibiotic pipeline from basic research through production. These vehicles have broad precedents and have demonstrated effectiveness at stimulating early stage scientific research. Current estimates show $550 million is spent annually on push spending, though some recommendations show that this number should be $800 million to fully meet the demand for antibiotic research[42]. However, push policies and spending do not completely address the major economic issues.

Figure 3:A combination of push and pull policies are necessary to generate conditions to revitalize the antibiotic pipeline. Currently, only push policies are implemented. Pull policies can de-link an antibiotic’s development from its economic success, which is projected to increase the development rate of antibiotics that society needs.

Pull Policies: The primary goal of push policies is to jump start research and development in antibiotic discovery, but issues remain with the current market structure for antibiotics. This is illustrated by the fact that companies are failing after bringing important antibiotics to market. For instance, the biopharmaceutical company Achaogen successfully developed the antibiotic plazomicin in 2018, but filed for bankruptcy the following year due to insufficient profits from plazomicin[43]. Why would a company that successfully brings a new antibiotic to market fail? Antibiotics are generally prescribed for short periods of time (usually under two weeks), modern health policies support reducing or delaying the use of new antibiotics, and the market lifetime of antibiotics is reduced due to the inevitable development of resistance[44].Overall, these realities minimize sales of the new antibiotic and thus the profits of the developing company. In response, policymakers have proposed pull policies to de-link the sales of the new antibiotic to the economic reward given to the developers, improving the economic viability of developing new antibiotics. These pull policies are supported by the Infectious Diseases Society of America[45]. By de-linking sales from economic reward, the revenue from a new antibiotic is not purely based on the sales volume of that antibiotic. For example, a market entry reward (MER) — a large monetary sum given to developers of novel antibiotics upon successful drug approval — can be used to partially or fully de-link the number of sales from the economic reward. Multiple groups, such as the Boston Consulting Group, have estimated that a $1 billion MER per antibiotic is sufficient, suggesting that this award amount would lead to twenty novel antibiotics for society over the next three decades[42, 46].

An important supplement to any MER policy is the antibiotic susceptibility bonus (ASB)[47]. The ASB rewards companies that develop antibiotics that are effective over long periods of time. As an antibiotic remains effective against target bacteria, companies receive monetary awards. This policy helps better align all stakeholders’ (companies, patients, hospitals, insurance networks) interests towards generating and maintaining effective antibiotics. Companies will no longer have an incentive to oversell antibiotics, as they will receive more money the longer their drug is effective. This supplemental policy could safeguard MERs against abuse, and incentivize the development of antibiotics that act in society’s best interest: to develop effective treatments for long periods of time.

Another potential pull policy is the long-term supply continuity model (LSCM)[42], which addresses how companies respond once market exclusivity for a drug ends due to patent expiration. Suppliers may respond to loss of market exclusivity by either manufacturing fewer units in the case of a modest market or by increasing sales through marketing and promotion. Both actions are detrimental to public health in the case of an antibiotic, either promoting antibiotic overuse or making it harder for people who need the antibiotic to get it. The LSCM addresses this by having a country or group of countries make an agreement with manufacturers to produce a predetermined amount of the respective antibiotic for a specified price. This model to generate a predictable supply of an antibiotic acts as a pull mechanism by making the market for novel, essential antibiotics more sustainable for manufacturers.

Pull policies also have some downsides. For one, pull policies only reward successful antibiotic discovery campaigns; the inherent risk in developing these drugs may still dissuade companies. Also, while push policies have been validated with real world results, pull policies have not been evaluated as extensively. To encourage companies to work in this area, push policies, as well as pull policies, are needed to lower the risk of failed discovery programs. To develop the new drugs that society needs, companies need funding to start research and development and economic incentives to take the drugs to market.

Conclusion Proliferation of antibiotic resistance in bacteria is a major public health problem that is only accelerating. This crisis is caused by overuse of existing antibiotic drugs and lagging development of new ones. To address the former, many US and international institutions are working to improve current diagnostic practices and adopt standards for responsible antibiotic use. Increasing funding for rapid diagnostics R&D, initiating educational programs, and mandating the adoption of comprehensive hospital antibiotic stewardship programs are possible ways to reduce antibiotic overuse. To encourage the development of novel antibiotic drugs, many organizations have also subsidized research and development in this area. Additional incentives are being pursued to improve the commercial viability of antibiotic development and protect drug developers from the risks of the antibiotic market. Antibiotic resistance is a major global health crisis, but with efforts to improve responsible use and end the almost 40-year drought of novel antibiotic drug discovery[48], we can take steps to prevent the next public health emergency. 4“The right of the people to be secure in their persons, houses, papers, and effects, against unreasonable searches and seizures, shall not be violated, and no warrants shall issue, but upon probable cause supported by oath or affirmation, and particularly describing the place to be searched, and the persons or things to be seized.”

Acknowledgements

We thank Erika Madrian for her input in shaping the manuscript.

Citation

Yee, E. H., Cheng, S. S., Knappe, G. A. & Moomau, C. A. Antibiotic resistance: How to prevent the next public health emergency. MIT Science Policy Review 1, 10-17 (2020).

A computational approach to cancer

Toni-Ann Nelson transformed remote summer research into an opportunity to learn a new set of tools for analyzing tumors.

Raleigh McElvery
August 20, 2020

Toni-Ann Nelson has wanted to find a cure for cancer ever since she was nine years old and lost her grandfather to the disease. “I remember thinking there must be something that the doctors and scientists were missing,” she recalls. “It just couldn’t be that complicated.” Now one semester away from earning her degree in molecular biology, Nelson is realizing cancer is just that — complicated. After conducting cancer research during MIT’s Summer Research Program in Biology (MSRP-Bio), she understands much more about the intricacies of tumors and metastasis. But she’s also glimpsed just how many cellular puzzles remain to be solved.

Growing up in Jamaica, Nelson enjoyed all her science classes, but preferred biology because she knew it would provide the foundation to probe cancer. She graduated as the valedictorian of her high school class, and earned a scholarship to Alcorn State University in Mississippi, where she began in the spring of 2017.

Alcorn doesn’t have any cancer research facilities, so Nelson secured a position as an undergraduate researcher in Yan Meng’s plant tissue culture lab. For three years, Nelson aimed to improve viral disease resistance in sweet potatoes. Even though she wasn’t conducting clinical research, she mastered key molecular biology techniques like PCR, gel electrophoresis, and tissue culture.

“Fundamental research is important because many times finding a cure requires starting with the basics, and understanding what’s going on inside the cell,” she says.

When Nelson was accepted into MSRP-Bio as a Gould Fellow and assigned to work in Tyler Jacks’ lab, she was elated to get her first hands-on cancer research experience. But in April 2020 — two months before the program was slated to begin — MIT’s campus temporarily shut down due to the COVID-19 pandemic, and MSRP-Bio 2020 became a remote learning experience.

As a result, Nelson and her MSRP-Bio cohort conducted their research from home. She took on a computationally-intensive project that was conducive to remote work and required taking an online quantitative methods class. In a manner of weeks, she learned an entirely new set of skills, including programming languages like Python.

“I always thought that I wouldn’t need those types of computational tools as part of my cancer research,” she explains. “But working at MIT was enlightening, because it showed me that they are key to understanding disease. I can definitely see myself using them on my own projects in the future.”

Pink and purple histology image
Light micrograph of a lung adenocarcinoma. Credit: Vasilena Gocheva/Jacks Lab, Koch Institute

The Jacks lab studies the genetic events that contribute to cancer, and Nelson’s project centered on lung adenocarcinoma. The predominant form of non-small cell lung cancer, it begins in alveolar type II (AT2) cells. Past studies showed that, as the tumor progresses, AT2 cells change state and lose their original identity. Nelson wanted to determine which genes and proteins underlie this evolution. Her analyses showed that genetic markers characteristic of AT2 cells tend to decrease over time, while markers denoting faster-growing “high grade” tumors become more prevalent.

“The kinetics of these gene expression changes that are happening early on are still poorly understood,” she explains. “It just goes to show how complicated this pathology is, which I find even more fascinating.”

Once researchers can pinpoint the genes and proteins that drive changes in cancer cell state, they’ll be better equipped to design drugs that target and prevent metastatic processes.

Although Nelson couldn’t visit the lab in person, as on-campus research slowly began ramping up again, her graduate student mentor Amanda Cruz would show her around during their video conference calls. Cruz also helped Nelson explore the scientific literature, choose studies for the lab’s journal club, and perform computational analyses.

Given the unprecedented circumstances, Nelson says having a solid support system was key to her success. Nelson and her MSRP cohort also relied on one another for encouragement, and were each assigned a graduate student “pal” for guidance outside of lab.

“The program catered to our every need, and it’s structured to ensure that someone will always check up on you if you’re feeling alone,” Nelson says. “I never expected to get so much from this experience, especially because I’m not physically on campus. But what I learned this summer was so much more than I could ever have anticipated.”

Her time in the Jacks lab has solidified her fervor for cancer research, and she intends to apply to cancer biology PhD programs in order to continue this line of inquiry. “I’ve realized there’s still so much more to learn,” she says, “but we’re getting there.”

Top image courtesy of Toni-Ann Nelson
Posted: 8.19.20