Collaborating Authors


2021 will be the year of MLOps


January is the customary time to make predictions on what the year holds in store. Working in partnership with companies across multiple industries that are looking to develop data science and AI skills in their workforce, I have a good vantage point on the trends that are developing across the realm of technology. In addition, I have published recent research with colleagues at Cambridge University about the challenges that face organizations with deploying machine learning. From this perspective, there is a clear picture forming that 2021 will be a turning point within leading businesses for making a priority of operationalizing AI. In fact, the second half of 2020 has seen a new crop of tools, platforms and startups receiving investment to provide solutions to this difficult problem.

Computer vision app allows easier monitoring of glucose levels


A computer vision technology developed by University of Cambridge engineers has now been integrated into a free mobile phone app for regular monitoring of glucose levels in people with diabetes. The app uses computer vision techniques to read and record the glucose levels, time and date displayed on a typical glucose test via the camera on a mobile phone. The technology, which doesn't require an internet or Bluetooth connection, works for any type of glucose meter, in any orientation and in a variety of light levels. It also reduces waste by eliminating the need to replace high-quality non-Bluetooth meters, making it a cost-effective solution. Working with UK glucose testing company GlucoRx, the Cambridge researchers have developed the technology into a free mobile phone app, called GlucoRx Vision.

Ones we've lost


Scientists, too, died in the pandemic. COVID-19 has made 2020 a cruel year for us all. As Science went to press, the global toll of the pandemic had already exceeded 1.6 million, a tragic number that includes scientists of all specialties, ages, and backgrounds. Behind the mind-numbing total are individuals, each a spark of ingenuity, imagination, and creative spirit. Because we can't do justice to every life lost, we've chosen only a few. In remembering them, we mourn the much larger losses for the scientific community—and the world. ### Li Wenliang Li Wenliang did not set out to be a hero. On 30 December 2019, the 33-year-old Wuhan Central Hospital ophthalmologist warned a small group of colleagues that cases of a severe acute respiratory syndrome–like illness had been confirmed in area hospitals. “Don't spread the word, let your family members take precautions,” he wrote in a brief message. Someone did spread the word, which went viral. Four days later, Li was called to a meeting with local police, who forced him to confess to spreading rumors. When the young doctor fell ill with COVID-19 less than 1 week later, he took to the microblogging website Sina Weibo to tell his story. Citizens were outraged at the officials' tactics. As Li's condition deteriorated in the early hours of 7 February, millions followed media updates on his condition. When his hospital confirmed his death shortly before 3 a.m., thousands of locked-down Wuhan citizens came to their high-rise windows, calling his name and grieving. He became “the face of COVID-19 in China,” independent social media expert Manya Koetse wrote on her What's on Weibo website. The outrage forced an investigation, and in March, officials formally exonerated Li and apologized to his family. Although his death shook a nation, Li was a modest man dedicated to his work. In one social media post, he apologized to his patients for being irritable, then added that he enjoyed his fried chicken dinner after “thinking about it all day.” Ten months after his death, more than 1.5 million people still follow Li's Weibo page. His final post, in which he finally reported testing positive for the COVID-19 virus weeks after infection, has drawn more than 1 million comments, with dozens more posted every day. Writers address Li as if he's an old friend, sharing their daily troubles and future hopes, calling him an inspiration, and sending birthday wishes. Many sent congratulations when his wife gave birth to their second son, about 4 months after Li died. In early February, Li was “a symbol of public anger against the failure of the Chinese system to address the COVID-19 pandemic,” says Steve Tsang, a political scientist who focuses on China at the SOAS University of London. As China brought the outbreak under control, that anger has largely dissipated. But in the eyes of the public, Li remains the hero he never set out to be. — Dennis Normile and Bian Huihui ### Gita Ramjee After finishing her Ph.D., epidemiologist Gita Ramjee made a decision that would change the course of her life—and many others. She paused her work on childhood kidney disease to explore whether vaginal microbicides could protect South African women from contracting HIV. It was 1994, and the world was at the height of the AIDS crisis: Few treatments were available, and no end was in sight. And women, especially sex workers, were being hit increasingly hard. The largely overlooked plight of these women “sparked her passion,” says Gavin Churchyard, CEO of the Aurum Institute, the HIV and tuberculosis prevention nonprofit where Ramjee was chief scientific officer. “She wouldn't just sit back and allow things to happen,” Churchyard says. “She would make them happen.” Ramjee, a fierce advocate for women's health, devoted the rest of her life to searching for ways to prevent HIV infection and providing them to the communities that needed them most. She held herself and colleagues to high standards, Churchyard says, pushing for excellence in an area of research that often had disappointing results. “She was a persevering and dedicated person,” says social scientist Neetha Morar, whom Ramjee mentored at the South African Medical Research Council (SAMRC). “Every time a negative result came through, she would get up and continue on.” Ramjee's commitment to work was matched only by her devotion to her family, Morar says. When her two sons still lived at home, she would prepare a full meal—with handmade bread—every day before work, to make sure her family ate dinner together in the evening. After her sons left home, Morar says, she kept up the ritual with her husband. She was ecstatic at the birth of her first grandchild and often brought pictures to the office to show colleagues, Churchyard remembers. Ramjee died on 31 March at age 63. Even months after her passing, her life's labor is still bearing fruit, says Wafaa El-Sadr, an epidemiologist at Columbia University and longtime collaborator. While at SAMRC, Ramjee oversaw on-site trials for a long-acting antiviral injection recently found to be more effective than a daily pill at preventing HIV in women. “She would have been thrilled,” El-Sadr says. “It's very bittersweet to have this amazing victory and she's not around to celebrate.” — Lucy Hicks ### Lynika Strozier Lynika Strozier lay in a hospital bed dying of COVID-19 as Black Lives Matter protesters took to the streets of Chicago in June. The 35-year-old geneticist was a gifted laboratory scientist, a passionate teacher, and a mentor to scores of students, many from underrepresented backgrounds. “Science was her baby,” says her grandmother, Sharon Wright, who raised Strozier from birth. Her path wasn't easy. Strozier was diagnosed early in life with a learning disability, and she had to study harder than her peers, Wright says. But she was a natural when it came to lab work, discovering her talent in college when she landed an internship taking care of cell lines at Truman College. “Most of us would have given up—and she always persevered,” says Matt von Konrat, a botanist at the Field Museum who watched Strozier move from intern to research assistant to collections associate at the museum's Pritzker DNA Laboratory, where she studied evolution in liverworts, birds, and other organisms. By 2018, Strozier had completed two master's degrees, one in biology and one in science education, before starting a job teaching ecology and evolution in January at Malcolm X College. “We had hoped that that would be just the beginning of her success story,” says Sushma Reddy, an evolutionary biologist at the University of Minnesota, Twin Cities, who was Strozier's graduate adviser at Loyola University Chicago. She was an inspiring teacher, Reddy says, and she was also someone her students could aspire to be. “She was literally the first Black scientist I ever met,” says Heaven Wade, a biochemistry undergraduate at Denison University whom Strozier mentored during an internship at the Field Museum. “We all loved her.” Wade, who is also Black, credits Strozier with keeping her in science: When she considered switching her major because she wasn't feeling “very welcome” in her program, Strozier persuaded her to stay. “She was so encouraging … it really inspired me to keep going.” Even now, Strozier continues to inspire young scientists. Her colleagues came up with the idea of creating an internship in her name, to help women of color gain research experience at the Field Museum. The fund is halfway to its $100,000 goal. “That's what Lynika would have wanted,” Reddy says. — Katie Langin ### John Houghton John Houghton loved a good country walk. So when the British climate scientist, instrumental to sounding the global alarm on climate change, found himself with a free afternoon at the National Center for Atmospheric Research's Mesa Laboratory near Boulder, Colorado, he headed straight out the back door—and into the Rocky Mountains. He even convinced a handful of fellow visitors, in inappropriate shoes, to join him as the sunlight waned. That spirit of exploration was fundamental to Houghton, who began his career in the 1960s developing space-based sensors that used the radiation emitted by carbon dioxide to take the atmosphere's temperature. Those measurements soon helped make clear that the burning of fossil fuels could, in a few generations, deeply alter the planet. In time, Houghton found himself in a position to make a difference, directing the United Kingdom's Met Office and helping lead the first three reports from the United Nations's Intergovernmental Panel on Climate Change (IPCC). Houghton was widely regarded as brilliant, but it was his emotional intelligence that made him so effective, says Robert Watson, a former IPCC chairman. “He showed respect for people,” Watson says. During the summit of the third IPCC assessment, published in 2001, government representatives spent the entire first day squabbling over a sentence that explained who was preparing the report. Fellow panelist David Griggs despaired of getting more controversial language approved. “Everyone wants to hear their own voice,” Houghton told him. “If I allow them to take control now, they'll allow me more flexibility later.” And sure enough, by the third day, the IPCC scientists were willing to include a sentence that is now seen as a turning point in climate science: “Most of the warming observed over the last 50 years is attributable to human activities.” Like many who led the charge on climate change, Houghton, who died in April at age 88, did not live to see the world mount a credible response. But he never lost faith in humanity, Griggs says. “He always felt, in the end, people would respond and act on climate change.” That optimism may have stemmed in part from Houghton's deep Christian faith, which led him to engage with climate change skeptics—and sometimes convince them, Watson says. The hikers who set off from the Mesa Lab that afternoon never made it to the summit, says Griggs, who was among them. A pitch-black night fell, and they were ready to bed down outside—but Houghton believed they'd find the road back. They did. — Paul Voosen ### Lungile Pepeta When the breadwinner of a Xhosa family dies, mourners say umthi omkhulu uwile , a mighty tree has fallen. That's what family, friends, and colleagues felt when Lungile Pepeta, a leading South African pediatric cardiologist and dean of health sciences at Nelson Mandela University, lost his life to COVID-19 at age 46, says Samkelo Jiyana, a pediatric cardiologist who trained under Pepeta, a tireless champion of rural and child health care. “He was an incredible person,” says pediatric cardiologist Adèle Greyling, who also trained under Pepeta. “It was a devastating loss for us all.” Pepeta, who grew up in Eastern Cape province, never forgot his roots. After his training in Johannesburg, he returned to the Eastern Cape, where he founded the poverty-stricken province's first pediatric cardiology unit and began to train others to follow in his footsteps. Before his arrival, children with serious heart conditions were forced to travel hundreds of kilometers—often by bus or even hitchhiking—to medical centers in major cities. Pepeta's research at Nelson Mandela University, in the Eastern Cape, focused on congenital heart conditions and rheumatic heart disease, which often arises from untreated streptococcal throat infections. It is a “disease of the poor,” says Jiyana, who now works at Netcare Greenacres Hospital in Port Elizabeth, South Africa. But when the pandemic reached the Eastern Cape, Pepeta launched a public information battle through social media and TV interviews in which he urged social distancing and the isolation of anyone who might be infected. He also called for coordination between the region's public and private health care systems and advised the provincial government on its pandemic response. Pepeta did not live to see the achievement of one of his most ambitious dreams: the opening of South Africa's 10th medical school, at his university. He deliberately located the school on the Missionvale campus—once an apartheid-era university built for Black people—to fulfill its mission of delivering “proper healthcare for all our communities,” he wrote last year. On his birthday on 16 July, Pepeta was in the hospital with COVID-19 symptoms when he received news that the medical school's accreditation application had been approved. Soon after, when he was already on high-flow oxygen and within days of being admitted to the intensive care unit, he submitted his final paper to a medical journal. He died on 7 August. “He did the work of two or three other people in his lifetime,” Greyling says. “I don't think we'll ever meet anyone like him again.” — Cathleen O'Grady ### Maria de Sousa When Portuguese immunologist Maria de Sousa was teaching at the University of Porto in the 1990s, she would take her students to the city's famous art museum, in a former 18th century palace. She would tell them to describe a painting, then take a second look. “She wanted to teach people how to see, because people miss what's there,” says Rui Costa, a neuroscientist at Columbia University and former student. De Sousa herself looked beyond the obvious in a career that took her to top research centers in the United Kingdom and New York City, then back to her home country. Her discoveries, and her tireless devotion to Portuguese science, earned her the status of a revered hero in the research community. She died in Lisbon, Portugal, on 14 April at age 80. De Sousa's work in immunology began in the 1960s, when a dictator ruled Portugal and most young women had no choice but to become homemakers. After earning a medical degree, de Sousa left at age 25 for graduate studies in London and Glasgow, U.K. There, she examined mice from which the thymus—an organ whose role in the immune system was just coming to light—had been removed soon after birth. A whole class of immune cells produced by the thymus was missing from the animals' lymph nodes. She realized that the cells, now called T cells, must migrate from the thymus to specific areas in the lymph nodes, where they stand ready to fight pathogenic invaders. The discovery soon became part of standard immunology textbooks. De Sousa moved to New York City in 1975 and later established a cell ecology lab at what is now Memorial Sloan Kettering Cancer Center. But she was drawn back to Portugal in 1984 to study hemochromatosis, an inherited disease common in the northern part of the country that causes a harmful overload of iron in the blood. De Sousa also had a second mission: to bring scientific rigor to Portugal's then-weak research institutions. She worked with the country's science minister to establish outside reviews of university research programs. And de Sousa pushed for Portugal's first graduate programs in biomedical science, including a highly regarded Ph.D. program that she led at the University of Porto. “She spearheaded a revolution in Portuguese science,” Costa says. De Sousa was not only a creative scientist and demanding mentor; she was also a poet, pianist, and art lover. “She was the quintessential intellectual,” Costa says. After her death, Portugal's president, Marcelo Rebelo de Sousa, remembered her as “an unmatched figure in Portuguese science.” — Jocelyn Kaiser ### Mishik Kazaryan and Arpik Asratyan In 1980, at the tender age of 32, experimental physicist Mishik Kazaryan won the Soviet Union's top science prize for his pioneering work on metal vapor lasers. At the same time, his wife—epidemiologist Arpik Asratyan—was making her own mark as a scientist, crisscrossing the vast nation and probing disease outbreaks. The high-achieving couple, who mentored scores of scientists, persevered through the Soviet collapse and the subsequent privations visited on Russian research. But within days of celebrating their 45th wedding anniversary, they succumbed to COVID-19: Asratyan first, on 27 March, and Kazaryan 10 days later. The couple ran a science-first household: Their daughter, Serine Kazaryan, is a gynecologist with the Global Medical System Clinic in Moscow, and their son, Airazat Kazaryan, is a gastrointestinal surgeon at the Østfold Hospital Trust in Grålum, Norway. Talk at the dinner table often revolved around research, and daughter, father, and mother published several papers together. Mishik Kazaryan, born in Armenia, spent his entire working life at one of Russia's scientific powerhouses, the P. N. Lebedev Physical Institute. His research spanned areas including high-power tunable lasers, laser isotope separation, and laser medicine; he collaborated with Alexander Prokhorov, who shared the 1964 Nobel Prize in Physics for the invention of the laser. Mishik Kazaryan's “major contribution,” Serine Kazaryan says, was a self-heating copper vapor laser—the brightest pulsed visible-light laser—that found wide use in the precision machining of semiconductors and other materials. Asratyan, also born in Armenia, first studied Mycoplasma hominis , a then–little-known bacterium linked to pelvic inflammatory disease, vaginosis, and respiratory ailments. She became a leading figure in the diagnosis of hepatitis B and C at the Gamaleya Research Institute of Epidemiology and Microbiology, and she spent much of her career working with vulnerable individuals: drug addicts and those with psychiatric afflictions or HIV. “I don't remember my parents to complain of anything,” says Serine Kazaryan, who lived with her son, daughter, and parents in an apartment in Moscow. They all took ill in mid-March. Serine Kazaryan and her children recovered. Her parents did not. Right up until his last days, Mishik Kazaryan was wrapping up a book about the laser cutting of glass. It was “very touching,” Serine Kazaryan says, when an old friend and co-author, Valery Revenko of the JSC Scientific Research Institute of Technical Glass, vowed to complete it. — Richard Stone ### Ricardo Valderrama Fernández Peruvian scientist and politician Ricardo Valderrama Fernández was first in many things. In the 1970s, he was among the first anthropologists to make contact with the Kugapakori, an Indigenous group living in the Peruvian Amazon. He co-founded the first research institute for Andean studies in Cusco in 1974. And in 1977, he wrote a “revolutionary” work on Indigenous, Quechua-speaking laborers, in which—breaking with anthropological traditions of the time—their testimony took center stage. The book, one of the first works on contemporary Andean culture, “broke the barrier” between anthropology and politics, says César Aguilar León, an anthropologist at the National University of San Marcos. Gregorio Condori Mamani: An Autobiography documented the poverty, discrimination, and mistreatment faced by those left behind in a society grappling with the legacy of Spanish colonialism. “We wanted to be the voice of those who are not heard, to write the words of those who cannot read and write,” says Valderrama Fernández's co-author and wife, anthropologist Carmen Escalante Gutiérrez. The couple always worked together and published four more books and dozens of articles on the legends and customs of the Andean people. They immersed themselves in remote communities and lived alongside Indigenous people for months. Valderrama Fernández's fluency in abstract Quechua, which included theological and philosophical concepts and terms, helped him speak freely with Andean elders and understand how they adapted their ancient cosmology to the present. His love of the language, which he learned from his grandmother, never diminished. “That's what made him special,” Escalante Gutiérrez says. Valderrama Fernández taught for 30 years at his alma mater, the National University of Saint Anthony the Abad in Cusco. In his final years, he embarked on a second career in politics, advocating for the region's Indigenous people. In 2006, he was elected to the municipal council of his hometown; in December 2019, he became interim mayor of Cusco, after his predecessor left office under a cloud of corruption charges. In his new role, Valderrama Fernández led the COVID-19 response in Cusco, visiting markets and other areas of the city to enforce health measures. He caught the virus on one of those visits, and died on 30 August at 75 years old. Jan Szemiński, a historian at the Hebrew University of Jerusalem, says the world has lost a great anthropologist—and someone who embodied the Incan ideal of reciprocity, or ayni : the idea that you should give to others today—knowing that tomorrow, you will receive. — Rodrigo Pérez Ortega ### John Horton Conway John Horton Conway liked to have fun. The U.K.-born mathematician cut a broad path, making important contributions to geometry, group theory, and topology. But unlike some great mathematicians who grind away on inscrutable problems in jealously guarded isolation, Conway—who worked at the University of Cambridge and Princeton University—was gregarious, talkative, and, above all, playful, often drawing deep insights from mathematical games. In the 1970s, while musing about the end stage of the board game Go, Conway expanded the concept of real numbers into something called “surreal numbers,” which are smaller or larger than any positive number. In 1985, he and four colleagues essentially wrapped up an entire subfield of math by identifying all groups with a finite number of elements. (A group is a closed set of elements and a rule akin to addition or multiplication for combining them—for example, all rotations that leave the image of a featureless cube the same.) Most famously, in 1970 Conway invented something he called the game of life. Imagine a grid of squares, some colored black for “living,” others colored white for “dead,” with rules for changing a square's color that depend on those of its neighbors. The simple system can produce a shocking variety of moving patterns depending on its initial configuration, and the game became popular as computers made their way into everyday life. Conway showed the squares could also be configured to do computations. As impressive as Conway's genius was his generosity of spirit, says Marjorie Senechal, a mathematician at Smith College. In the 1990s, she helped organize summer geometry institutes to build bridges among professional mathematicians, math teachers, and students. The first few summers, the pros simply lectured the others, Senechal says. Then she invited Conway, and everything clicked. “He didn't see these as separate communities,” she says. “He was like the Pied Piper. He'd go to get a coffee and a hundred people would follow him.” Conway, who died in April at age 82, would prowl the Princeton math department at night, chatting with anyone he could find about his latest interest, recalls Timothy Hsu, a mathematician at San Jose State University who earned his doctorate with Conway in 1995. Unkempt and funny, Conway studiously ignored his mail, but could be reached by phone—in the department common room. “Towards the end of my graduate career, he told me that because math is such a forbidding subject, it helps to make yourself slightly ridiculous,” Hsu says. Conway then teased, “That seems to come naturally to you.” — Adrian Cho ### Donald Kennedy Neurobiologist Donald Kennedy brought a towering intellect, insatiable curiosity, and abiding interest in both the concerns of individuals and the fate of society to everything he did. The longtime faculty member and former president of Stanford University “could talk to people about science without condescending to them,” says research advocate Thomas Grumbly, a friend and colleague. “And he could stand toe to toe with the best scientists in the world.” Kennedy, who died on 21 April at age 88, relished his role as a scientist, educator, public servant, and communicator—even when his views did not prevail. After Congress refused to embrace his proposed ban on the artificial sweetener saccharine while he was commissioner of the U.S. Food and Drug Administration in the late 1970s, he questioned its logic. The body had “established a principle,” Kennedy said. “You shouldn't have cancer-causing substances in the food supply, unless people like them a lot.” That dry wit did him no favors in a subsequent fight with a congressional panel investigating Stanford's questionable use of federal research funds during his tenure as president. The fallout from that grueling inquiry led him to step down from the presidency in 1991. In 2000, Kennedy became editor-in-chief of Science . He used the platform to prod climate researchers to work harder on public outreach, condemn politicians who bent—or ignored—scientific findings to serve their own purposes, and publish the best research on the planet, including the first sequence of the human genome. Kennedy had been a larger-than-life figure at Stanford, whether dashing around campus on his bike or posing bare-chested with the championship swim team. He brought that enthusiasm to the journal, where he also liked to shine a light on the personal side of science. One of his editorials accompanied a 2005 paper describing a sighting of the ivory-billed woodpecker, long thought to be extinct. Kennedy recounted how, at age 7, he wrote a “fan letter” to famed Cornell University ornithologist Arthur Allen about Allen's pursuit of the fabled bird. The letter, signed “Love, Donny,” prompted a reply that ended “Love, Arthur.” The woodpecker sighting didn't hold up to scrutiny. But Kennedy's point did: that an encouraging word from a senior scientist could have a lasting impact on a curious child. In fact, one could say Kennedy spent his entire career paying forward that kindness. — Jeffrey Mervis

Hey Alexa, what's my PIN? Voice assistants can figure out the taps made on a smartphone keyboard

Daily Mail - Science & tech

Smart speakers like Google Home and Amazon Alexa could be used by criminals to listen to and decipher a password or PIN being typed in on a nearby phone. Researchers from the University of Cambridge built their own version of a smart speaker to closely resemble those which are commercially available. Sound recordings from the gadget were inputted into a computer for analysis and experts investigated if the sound and vibrations caused by typing on a smartphone screen could be used to guess a five-digit passcode. When the phone was placed within 20cm (7.8inches) of the custom-built device, the computer was able to guess the code with 76 per cent accuracy in three attempts. This graphic outlines the general flow of the experiment.

Cambridge University launches master's degree in responsible use of AI


While AI is popularised in science fiction by killer robots – such as The Terminator – it is now in everyday use in forms such as Amazon's Alexa virtual …

Voice assistant recordings could reveal what someone nearby is typing

New Scientist

Voice assistants can detect typing on nearby devices, which could potentially be used to work out what a person is writing on their phone from up to half a metre away. Ilia Shumailov at the University of Cambridge and his colleagues built a machine-learning system that could recognise the sound of tapping on a touchscreen and combined it with other artificial intelligence tools to try to determine what people were typing.

Tracking development at the cellular level


We each developed from a single cell—a fertilized egg—that divided and divided and eventually gave rise to the trillions of cells, of hundreds of types, that constitute the tissues and organs of our adult bodies. Advancing our understanding of the molecular programs underlying the emergence and differentiation of these diverse cell types is of fundamental interest and will affect almost every aspect of biology and medicine. Recently, technological advances have made it possible to directly measure the gene expression patterns of individual cells ([ 1 ][1]). Such methods can be used to clarify cell types and to determine the developmental stage of individual cells ([ 2 ][2]). Single-cell transcriptional profiling of successive developmental stages has the potential to be particularly informative, as the data can be used to reconstruct developmental processes, as well as characterize the underlying genetic programs ([ 3 ][3], [ 4 ][4]). ![Figure][5] A genomic technique for tracking cellular development High-throughput single-cell genomic methods enable a global view of cell type diversifcation by transcriptome and epigenome CREDIT: N. DESAI/ SCIENCE FROM CAO ET AL. ([7][6]) AND BIORENDER When I began my doctoral studies in Jay Shendure's lab at the University of Washington, available single-cell sequencing techniques relied on the isolation of individual cells within physical compartments and thus were limited in terms of both throughput and cost. As a graduate student, I developed four high-throughput single-cell genomic techniques to overcome these limitations ([ 5 ][7]–[ 8 ][8]). Leveraging these methods, I profiled millions of single-cell transcriptomes from organisms, in species that included worms, mice, and humans. By quantifying the dynamics of embryonic development at single-cell resolution, I was able to map out the global genetic programs that control cell proliferation and differentiation at the whole-organism scale. By the 1980s, biologists had documented every developmental step in the nematode Caenorhabditis elegans , from a single-cell embryo to the adult worm, and mapped the connections of all of the worm's neurons ([ 9 ][9]). However, although the nematode worm has a relatively small cell number (558 cells at hatching), a comprehensive understanding of the molecular basis for the specification of these cell types remains difficult. To resolve cellular heterogeneity, I first developed a method to specifically label the transcriptomes of large numbers of single cells, which we called sci-RNA-seq (single-cell combinatorial indexing RNA sequencing) ([ 5 ][7]). This method is based on combinatorial indexing, a strategy using split-pool barcoding of nucleic acids to label vast numbers of single cells within a single experiment ([ 9 ][9]). In this study, I profiled nearly 50,000 cells from C. elegans at the L2 stage, which is more than 50-fold “shotgun cellular coverage” of its somatic cell composition. We further defined consensus expression profiles for 27 cell types and identified rare neuronal cell types corresponding to as few as one or two cells in the L2 worm. This was the first study to show that single-cell transcriptional profiling is sufficient to separate all major cell types from an entire animal. C. elegans development follows a tightly controlled genetic program. Other multicellular organisms, such as mice and humans, have much more developmental flexibility. However, conventional approaches for mammalian single-cell profiling lack the throughput and resolution to obtain a global view of the molecular states and trajectories of the rapidly diversifying and expanding cell types. To investigate cell state dynamics in mammalian development, I developed an even more scalable single-cell profiling technique, sci-RNA-seq3 ([ 7 ][6]), and used it to trace the development path of 2 million mouse cells as they traversed diverse paths in a 4-day window of development corresponding to organogenesis (embryonic day 9.5 to embryonic day 13.5). From these data, we characterized the dynamics of cell proliferation and key regulators for each cell lineage, a potentially foundational resource for understanding how the hundreds of cell types forming a mammalian body are generated in development. This was, and remains, the largest publicly available single-cell transcriptional dataset. The sci-RNA-seq3 method enabled this dataset to be generated rapidly, within a few weeks, by a single individual. A major challenge regarding current single-cell assays is that nearly all such methods capture just one aspect of cellular biology (typically mRNA expression), limiting the ability to relate different components to one another and to infer causal relationships. Another technique that I developed, sci-CAR (single-cell combinatorial indexing chromatin accessibility and mRNA) ([ 6 ][10]), was created with the goal of overcoming this limitation, allowing the user to jointly profile the epigenome (chromatin accessibility) and transcriptome (mRNA). I applied sci-CAR to the mouse whole kidneys, recovering all major cell types and linking cis-regulatory sites to their target genes on the basis of the covariance of chromatin accessibility and transcription across large numbers of single cells. To further explore the gene regulatory mechanisms, I invented sci-fate ([ 8 ][8]), a new method that identifies the temporal dynamics of transcription by distinguishing newly synthesized mRNA transcripts from “older” mRNA transcripts in thousands of individual cells. Applying the strategy to cancer cell state dynamics in response to glucocorticoids, we were able to link transcription factors (TFs) with their target genes on the basis of the covariance between TF expression and the amount of newly synthesized RNA across thousands of cells. In summary, my dissertation involved developing the technical framework for quantifying gene expression and chromatin dynamics across thousands to millions of single cells and applying these technologies to profile complex, developing organisms. The methods that I developed enable such projects to be achievable by a single individual, rather than requiring large consortia. Looking ahead, I anticipate that the integration of single-cell views of the transcriptome, epigenome, proteome, and spatial-temporal information throughout development will enable an increasingly complete view of how life is formed. GRAND PRIZE WINNER Junyue Cao Junyue Cao received his undergraduate degree from Peking University and a Ph.D. from the University of Washington. After completing his postdoctoral fellowship at the University of Washington, Junyue Cao started his lab as an assistant professor and lab head of single-cell genomics and population dynamics at the Rockefeller University in 2020. His current research focuses on studying how a cell population in our body maintains homeostasis by developing genomic techniques to profile and perturb cell dynamics at single-cell resolution. CATEGORY WINNER: ECOLOGY AND EVOLUTION Orsi Decker Orsi Decker completed her undergraduate degree at Eötvös Loránd University in Budapest, Hungary. She went on to receive her master's degree in Ecology and Evolution at the University of Amsterdam. Decker completed her doctoral research at La Trobe University in Melbourne, Australia, where she investigated the extinctions of native digging mammals and their context-dependent impacts on soil processes. She is currently a postdoctoral researcher at La Trobe University, where she is examining how land restoration efforts could be improved to regain soil functions through the introduction of soil fauna to degraded areas. [][11] CATEGORY WINNER: MOLECULAR MEDICINE Dasha Nelidova Dasha Nelidova completed her undergraduate degrees at the University of Auckland, New Zealand. She completed her Ph.D. in neurobiology at the Friedrich Miescher Institute for Biomedical Research in Basel, Switzerland. Nelidova is currently a postdoctoral researcher at the Institute of Molecular and Clinical Ophthalmology Basel, where she is working to develop new translational technologies for treating retinal diseases that lead to blindness. [][12] CATEGORY WINNER: CELL AND MOLECULAR BIOLOGY William E. Allen William E. Allen received his undergraduate degree from Brown University in 2012, M.Phil. in Computational Biology from the University of Cambridge in 2013, and Ph.D. in Neurosciences from Stanford University in 2019. At Stanford, he worked to develop new tools for the large-scale characterization of neural circuit structure and function, which he applied to understand the neural basis of thirst. After completing his Ph.D., William started as an independent Junior Fellow in the Society of Fellows at Harvard University, where he is developing and applying new approaches to map mammalian brain function and dysfunction over an animal's life span. [][13] 1. [↵][14]1. D. Ramsköld et al ., Nat. Biotechnol. 30, 777 (2012). [OpenUrl][15][CrossRef][16][PubMed][17] 2. [↵][18]1. C. Trapnell , Genome Res. 25, 1491 (2015). [OpenUrl][19][Abstract/FREE Full Text][20] 3. [↵][21]1. D. E. Wagner et al ., Science 360, 981 (2018). [OpenUrl][22][Abstract/FREE Full Text][23] 4. [↵][24]1. K. Davie et al ., Cell 174, 982 (2018). [OpenUrl][25][CrossRef][26][PubMed][27] 5. [↵][28]1. J. Cao et al ., Science 357, 661 (2017). [OpenUrl][29][Abstract/FREE Full Text][30] 6. [↵][31]1. J. Cao et al ., Science 361, 1380 (2018). [OpenUrl][32][Abstract/FREE Full Text][33] 7. [↵][34]1. J. Cao et al ., Nature 566, 496 (2019). [OpenUrl][35][CrossRef][36][PubMed][37] 8. [↵][38]1. J. Cao, 2. W. Zhou, 3. F. Steemers, 4. C. Trapnell, 5. J. Shendure , Nat. Biotechnol. 38, 980 (2020). [OpenUrl][39][CrossRef][40][PubMed][41] 9. [↵][42]1. D. A. Cusanovich et al ., Science 348, 910 (2015). 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Brain mapping, from molecules to networks


CATEGORY WINNER: CELL AND MOLECULAR BIOLOGY William E. Allen William E. Allen received his undergraduate degree from Brown University in 2012, M.Phil. in Computational Biology from the University of Cambridge in 2013, and Ph.D. in Neurosciences from Stanford University in 2019. At Stanford, he worked to develop new tools for the large-scale characterization of neural circuit structure and function, which he applied to understand the neural basis of thirst. After completing his Ph.D., William started as an independent Junior Fellow in the Society of Fellows at Harvard University, where he is developing and applying new approaches to map mammalian brain function and dysfunction over an animal's life span. [ ][1] Charting what the pioneering neuroanatomist Santiago Ramón y Cajal called the “impenetrable jungle” of the brain ([ 1 ][2]) presents one of biology's greatest challenges. How do billions of neurons, wired through trillions of connections, work together to produce cognition and behavior? Like an orchestra, wherein many instruments played simultaneously produce a sound greater than the sum of its parts, thought and behavior emerge from communication between ensembles of molecularly distinct neurons distributed throughout vast neural circuits. Although we know much about the properties of individual genes, cells, and circuits (see the figure, panel A), a vast gap lies between the function of each brain component and an animal's behavior. Bridging this gap has proven technically and conceptually difficult. Inspired by the fact that the development of high-throughput DNA sequencing led geneticists to shift focus from individual genes to the entire genome, I wanted to develop approaches that could simultaneously link multiple levels of the brain, from molecules to neurons to brain-wide neural networks. My goal was to capture a global perspective while maintaining the high resolution and specificity necessary to understand the function of individual components at each level. This new viewpoint, I hoped, would reveal how the collective properties of the brain's building blocks give rise to behavior. During my doctoral studies at Stanford University with Karl Deisseroth and Liqun Luo, I developed new methods to map the architecture and activity of mammalian neural circuits. I applied these approaches to understand the neural basis of thirst, a fundamental regulator of behavior ([ 2 ][3]). Need-based motivational drives, such as hunger and thirst, direct animals to satisfy specific physiological imperatives important for survival ([ 3 ][4]). Despite decades of research, at the beginning of my studies it was unclear how the activity of neurons that sense these needs causes an animal to engage in specific motivated behaviors (e.g., eating or drinking) to maintain homeostasis ([ 3 ][4]). Thirst, a relatively simple yet important drive, thus seemed the perfect model system for investigating multiple levels in the brain. I first traced thirst motivational drive from cellular gene expression to a circuit mechanism. Using a new version of targeted recombination in active populations (TRAP2), a tool to genetically label neurons according to their activity, I found that neurons in the median preoptic nucleus (MnPO) of the hypothalamus became activated in thirsty mice ([ 4 ][5]) (see the figure, panel C). Single-cell RNA sequencing revealed that these neurons formed a single molecularly defined cell type. Artificial activation of these neurons caused mice to drink water within seconds, whereas their inhibition prevented mice from drinking, which suggested that these MnPO neurons were master regulators of thirst. Drinking water also gradually reduced the activity of these neurons. Finally, activation of these neurons was aversive. Together, these results suggested a surprising “drive reduction” model of thirst motivation: Genetically hard-wired thirst neurons become active when mice need hydration, which causes mice to drink water. This ability to ascribe specific functional relevance to genetically defined neurons inspired me to develop new techniques to map cells within their native tissue architecture in even greater molecular detail. To this end, I co-developed STARmap, an approach for highly multiplexed in situ RNA sequencing to measure the expression of hundreds of genes simultaneously within a brain section at the level of single mRNA molecules ([ 5 ][6]) (see the figure, panel B ). In combination with genetic markers of activity, this technique powerfully describes the molecular identity of behaviorally activated neurons and their neighbors at single-cell resolution. ![Figure][7] New large-scale, high-resolution approaches to bridging multiple levels of brain function A new approach to brain function mapping. (A) An illustration of the levels of brain function and how they are interlinked. (B to D) New approaches to bridging levels: (B) STARm ap amplicons barcoding 1020 RNA species simultaneously with single-molecule resolution in the mouse visual cortex. (C) Genetic labeling of neurons according to activity reveals thirst neurons in the median preoptic nucleus of the hypothalamus, used to identify the motivational mechanism of thirst drive. (D) Brain-wide activity map of the response of thousands of neurons across dozens of brain regions to a water-predicting sensory cue, in thirsty or sated mice, reveals widespread broadcasting of thirst state. GRAPHIC: N. DESAI/ SCIENCE FROM W. ALLEN, WANG ET AL . ([ 5 ][6]), ALLEN ET AL . ( 4 ), ALLEN ET AL . ([ 9 ][8]) Despite these insights, a question remained: How do thirst-sensitive neurons deep in the brain coordinate activity in distributed circuits spanning sensory perception, cognition, and motor output to produce motivated behavior? I found that MnPO thirst neurons projected to many brain regions potentially serving different behavioral roles ([ 4 ][5]), but the gap between individual neurons and brain-wide networks was daunting. Earlier in graduate school, I had developed several new microscopy techniques to characterize brain-wide ([ 6 ][9]) or neocortex- wide ([ 7 ][10]) activity, which revealed that global neural activity was present during even simple motivated behaviors. However, because of the mammalian brain's opacity, these approaches were limited in their ability to record fast neural activity throughout the brain at the scale required to understand thirst motivation. Fortunately, however, developments in microelectronics enabled me to construct global maps of neuronal activity with microsecond-level temporal resolution. Using advanced “Neuropixels” probes ([ 8 ][11]), thin silicon needles that can be acutely inserted into the brain to record the electrical signals of hundreds of neurons simultaneously, I developed an experimental approach to record the activity of huge neuronal ensembles across the brain and reconstruct the anatomical location of each recorded cell ([ 9 ][8]). Applying this technique, I mapped the brain-wide flow of activity through ∼24,000 single neurons during thirst-motivated behavior ([ 9 ][8]) (see the figure, panel D). My experiments revealed that this simple behavior produced an unexpectedly global coordination of activity throughout the brain. By observing how activity changed as mice drank water, as well as directly stimulating hypothalamic thirst neurons, I showed that this activity wave was dependent on the animal's motivational state. Surprisingly, the activity of a few hundred thirst neurons instantly modulated the state of the entire brain. Even more surprisingly, I found many neurons, distributed throughout the brain, that directly encoded thirst. These results suggest that even simple behaviors, such as thirst, are emergent properties of the entire brain. I hope these new approaches will at last enable us to comprehend the rules that transform distributed patterns of electrical activity in neural circuits into thoughts, emotions, and perceptions. Understanding how molecules, neurons, and networks interact to shape these rules will have a sweeping impact on our understanding of brain function in health and disease. 1. [↵][12]“Mas, por desgracia, faltábanos el arma poderosa con que descuajar la selva impenetrable de la substancia gris…” ([ 10 ][13]). 2. [↵][14]1. C. A. Zimmerman, 2. D. E. Leib, 3. Z. A. Knight , Nat. Rev. Neurosci. 18, 459 (2017). [OpenUrl][15][CrossRef][16][PubMed][17] 3. [↵][18]1. S. M. Sternson , Neuron 77, 810 (2013). [OpenUrl][19][CrossRef][20][PubMed][21][Web of Science][22] 4. [↵][23]1. W. E. Allen et al ., Science 357, 1149 (2017). [OpenUrl][24][Abstract/FREE Full Text][25] 5. [↵][26]1. X. Wang et al ., Science 361, eaat5691 (2018). [OpenUrl][27][Abstract/FREE Full Text][28] 6. [↵][29]1. L. Ye et al ., Cell 165, 1776 (2016). [OpenUrl][30][CrossRef][31][PubMed][32] 7. [↵][33]1. W. E. Allen et al ., Neuron 94, 891 (2017). [OpenUrl][34][CrossRef][35][PubMed][36] 8. [↵][37]1. J. J. Jun et al ., Nature 551, 232 (2017). [OpenUrl][38][CrossRef][39][PubMed][40] 9. [↵][41]1. W. E. Allen et al ., Science 364, eeav3932 (2019). [OpenUrl][42] 10. [↵][43]1. S. Ramón y Cajal , Recuerdos de mi vida: Historia de mi labor científica (Moya, Madrid, 1917). 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Artificial Intelligence in Radiology: The Computer's Helping Hand Needs Guidance


See also the article by Tadavarthi et al in this issue. Evis Sala, MD, PhD, is the professor of oncological imaging at the University of Cambridge, UK and co-leads the Advanced Cancer Imaging Programme and the Integrative Cancer Medicine Programme for the Cancer Research UK Cambridge Centre. Her current research focuses on radiogenomics through multiomics data integration for evaluation of spatial and temporal tumor heterogeneity and on the applications of AI methods for image reconstruction, segmentation, and data integration. Stephan Ursprung, MD, is a 3rd-year PhD student in the department of radiology at the University of Cambridge, UK. His research focuses on the development of AI models for automated segmentation, lesion classification, and treatment response prediction in renal cancer. Dr Ursprung's interests include health information technology, molecular and physiologic imaging, as well as multiomics data integration.

Internet of Medical Things is Beginning to Transform Healthcare


The impact of AI on personal healthcare is attracting wide comment. "AI is transforming every industry in which it is implemented, with its impact upon the healthcare sector already saving lives and improving medical diagnoses," stated Dr. Ian Roberts, Director of Therapeutic Technology at Healx, a biotechnology company based in Cambridge, England, in an account in BBH (Building Better Healthcare). "The transformative effect of AI is set to switch healthcare on its head, as the technology leads to a shift from reactive treatments targeting populations to proactive prevention tailored to the individual patient."