2016 Vilcek Prize Recipients
The Vilcek Prize in Biomedical Science
Dan R. Littman, M.D., Ph.D.
The road to scientific stardom is often long and arduous, and fame is frequently reserved for those who relish the journey as much as its destination. From the early days of his career as an enfant brillant of immunology to his current role as an undisputed leader in the field, Dan Littman, a professor of molecular immunology at New York University’s Skirball Institute for Biomolecular Medicine, has derived a singular thrill in unraveling the human immune system’s intertwined networks. Over a career spanning more than three decades, Littman has uncovered crucial steps in the pathogenesis of HIV and unveiled the interactions between the immune system and the human body’s resident microbes.
Littman was born in the Romanian capital of Bucharest, a city smothered by the Communist ruler Nicolae Ceausescu in the 1960s. Born to educated parents who decided to escape the similarly oppressive Stalinist rule that preceded Ceausescu, Littman immigrated with his family to the United States when he was 11 years old. As a child, he was enthralled by the workings of mechanical devices, and he resolved to become an aerospace engineer. After graduating high school, Littman promptly enrolled at Princeton University to pursue his passion. But he was soon enticed by molecular biology, a field whose scientific ferment suggested novel ways to explore the workings of life itself. Before long, he dropped engineering to focus on biology, joining the lab of cell biologist Marc Kirschner to perform undergraduate research.
The experience whetted Littman’s appetite for basic science and set him on a career path that has wended through some of the world’s premier destinations for biological research. Beginning at Washington University School of Medicine in St. Louis, where he enrolled for an M.D./Ph.D. program in 1974, Littman set his sights on the mechanics of the immune system. His doctoral work on the recognition of foreign antigens by the immune system may not have yielded revolutionary insights, but it honed the skills that readied him for his lifelong pursuits. On that foundation, he built a towering edifice of scientific knowledge that has helped tease apart the genetic basis of immune responses and paved the way for the treatment of HIV and autoimmune diseases.
Those gains can be traced back to Littman’s apprenticeship with Columbia University molecular biologist Richard Axel, with whom he began postdoctoral studies in 1981. In Axel’s lab, Littman embraced a then-novel technique for transferring genes into mammalian cells to parse their functions. Launched with the goal of isolating genes involved in antigen recognition, his efforts yielded findings now firmly lodged in the bedrock of immunology. He isolated the genes encoding proteins that confer immunological identity to the two main types of cells in the human immune arsenal: the CD4 protein, which dots the surface of helper T cells, and the CD8 protein, which adorns killer T cells.
Around the time Littman joined Axel, the AIDS epidemic in the United States began its inexorable march, felling scores of infected men in far-flung cities, baffling the medical establishment with its mysterious etiology, and ultimately sweeping the country into a sociopolitical drama driven by death and collective despair. Before long, HIV was revealed to be the cause of AIDS, and the human immune system’s helper T cells were fingered as the primary targets of the virus. In the wake of those findings, researchers began a frantic search for the handholds of the virus on T cells. Littman’s team began by testing the role of CD4 in viral infection. “We initially tested the requirement for CD4 for the virus to infect T cells. But CD4 alone did not work in mouse cells,” Littman says. Working alongside other researchers, Littman found in 1996 that HIV hijacks a protein called CCR5 on the surface of helper T cells to gain entry into the immune system. “Binding to CD4 exposes a region of the viral envelope glycoprotein, allowing it to bind to CCR5,” explains Littman. A decade after his discovery, the Food and Drug Administration approved the HIV drug maraviroc, which blocks the interaction of HIV with CCR5, now known in scientific parlance as a co-receptor for HIV. (Despite their continued use in some antiretroviral cocktails, CCR5-blocking drugs have since been overshadowed by more potent drugs that block viral protease enzymes.)
Littman’s findings also paved the way for the discovery of rare but natural genetic variations in CCR5 that render some people resistant to the virus. The now-famous “Berlin patient,” an HIV-infected American man thought to be rid of the virus thanks to a bone marrow transplant he received from a donor with infection-hobbling CCR5 mutations, is a case in point. Efforts to treat HIV through transplantation of T cells with engineered CCR5 mutations are underway.
In 1985, Littman moved to the University of California, San Francisco, to accept an assistant professorship in immunology. At UCSF, he probed the genetic basis of the immune system’s exquisite specificity. His team uncovered a genetic element known as a silencer that plays a crucial role in shaping the molecular identity of CD4 cells, as well as the immunological signaling pathways in which CD4 and CD8 molecules participate along with the T cell antigen receptor.
In 1995, he returned to New York City to accept a professorship in molecular immunology upon the urging of the late virologist Lennart Philipson, founding director of the Skirball Institute. There, extending work begun earlier, Littman’s team uncovered a group of gene switches called Runx proteins, which offered a key to the long-puzzling question of how immature precursors of T cells mature into helper and killer T cells in the thymus gland. These precursors, which harbor both CD4 and CD8 molecules on their surface, undergo a process of selective pruning to give rise to helper or killer T cells. By silencing the genes for CD4 molecules in precursor cells destined to become killer T cells, Runx proteins, Littman’s team found, influence the immunological identities of the immune system’s foot soldiers.
Taking a similar tack, Littman’s team later uncovered a gene switch called RORgammat, which shapes the development of a subset of helper T cells called Th-17 cells, which abound in the intestines. There, Th-17 cells secrete the immune molecule IL17, implicated in a range of conditions such as arthritis, psoriasis, and ankylosing spondylitis. In short order, preclinical studies of psoriasis suggested a protective role for compounds that block RORgammat, which has since become a drug target for autoimmune diseases.
More recently, Littman and his collaborators unearthed yet more fundamental insights on Th-17 cells. They found that the abundance of Th-17 cells in the gut is tied to the presence of gut microbes called segmented filamentous bacteria. When exposed to the bacteria, mice experimentally denuded of Th-17 cells produced a profusion of the cells, mounted a protective immune response, and fended off an intestinal pathogen. However, the mice also became more susceptible to Th-17-mediated autoimmune diseases, such as arthritis. Spurred by this finding, Littman’s team examined the gut microbiota in patients with rheumatoid arthritis, a debilitating autoimmune disease, and found a much higher proportion of patients than healthy individuals who harbored the human intestinal bacterium Prevotella copri. The results, combined with rodent studies, raise the possibility of a preliminary—but as yet unestablished—link between the abundance of P. copri and the risk of rheumatoid arthritis. Collectively, these findings have led to a growing realization that altering the human gut microbiome might lead to ways to curb and counter inflammatory and autoimmune diseases.
Over a long and distinguished career, Littman has straddled disciplines in a bid to find the organizing principles behind the human immune system’s byzantine networks. Along the way, his work has yielded a wealth of promising clinical leads. He attributes his success to the scientific environment in the United States, where basic researchers are cosseted and unbridled exploration is fostered. “What makes doing research in the United States so unique is that there is so much freedom. In many parts of the world, researchers work in hierarchical settings and are constrained by the kinds of questions they can ask. I was fortunate in getting into science in this country from the very beginning. There are many talented young people in eastern European countries who don't have the same opportunities to pursue their dreams,” he adds.
The Vilcek Prize in Theatre
Blanka Zizka never imagined that she would become one of the American theatre’s leading lights when she first arrived in the U.S. in 1977. But today she is the highly respected artistic director of the Wilma Theater, which under her care has grown into one of the nation’s most prestigious stages and a cultural anchor for Philadelphia. Her accomplished work as a director and producer has led her to champion and interpret some of the most challenging voices in contemporary drama. Her adventurous spirit and her dedication to craft have inspired collaborators and audiences, who turn to her as a teacher, advocate, and beacon. Zizka’s productions do not have a uniform aesthetic, but instead reflect her abiding interest in the largest humanist questions—onstage ontologies always rooted in the political and emphasizing the actor’s body and process.
Born in Communist Czechoslovakia, Blanka Vanickova grew up in a family who valued education and the arts, taking her to dance and acting classes. Upon leaving school, her refusal to join the Communist Party limited her options, but she began working in Prague’s underground theatres alongside Jiri Zizka, then her boyfriend, later her partner in work and marriage. (Jiri Zizka died in 2013.) Harassment and arrests of independent artists were common; when their activities were discovered and closed down, they felt ready to leave. When she was just 21, the couple had an opportunity to travel to Germany; it was a rare window. Risking everything and worried about the implications for their families at home, they crossed the border on a frightening train journey, immediately applying for political asylum.
“We didn’t know anything; we were so uninformed in Czechoslovakia, so isolated,” says the director. “We thought that we would go to France or Italy or England. We learned that once you apply for political asylum you have to stay in that country, because nobody wants immigrants.” After living as refugees for more than a year, Zizka (then pregnant with her son Krystof) came to the United States, arriving in Philadelphia. Although her English was limited, she began teaching movement workshops with the Wilma Project, a fledgling performance group. In 1979 she and Jiri staged a now-legendary version of George Orwell’s novella Animal Farm with the company, and in 1981 the pair co-founded the Wilma Theater.
The artists made a home in an intimate theatre on Sansom Street in Center City Philadelphia, with low ceilings and only 100 seats. But the intensity and inventiveness of the Wilma’s offerings attracted a loyal audience. Since founding the organization, Zizka has directed more than 60 productions for the company. From the outset, the Wilma became known for its commitment to ambitious works from the modern and contemporary international repertory rarely seen elsewhere in the U.S. Among Zizka’s most celebrated stagings were deeply polemical works by South Africa’s Athol Fugard and Chile’s Ariel Dorfman (whose play The Other Side she mounted at New York’s Manhattan Theatre Club with Rosemary Harris and John Cullum).
She also developed close working relationships with figures as important as the dissident playwright (and later Czech president) Vaclav Havel and the Czech-born British author Tom Stoppard. (Zizka first championed and then premiered Stoppard’s master epic The Invention of Love to critical acclaim prior to its international success.)
Among the many plays, musicals, and operas she has staged, Zizka is also proud of her 1995 production of Road, Jim Cartright’s stark evocation of economic anguish. Her potent physical dynamism won Philadelphia’s Barrymore Award, and the piece became the first American theatre production to tour to the Czech Republic’s International Theatre Festival. Her kinetic, committed collaborations with challenging American dramatists such as Dael Orlandersmith (author of Raw Boys and Yellowman) have steadily garnered attention, winning her the Zelda Fichandler Award from the Stage Directors and Choreographers Foundation in 2011.
In 1996, the Wilma moved to a new 296-seat facility on Philadelphia’s Avenue of the Arts, symbolically placed at the geographical heart of the city. The building confirmed the organization’s importance in a region whose once-dormant theatre scene was now thriving. Despite this local success, Zizka says, national recognition has proven harder to come by. “It’s not so easy to gain national recognition when you are not working in New York or Chicago,” she says.
While Zizka has founded and nourished one of America’s most successful resident theatres, she has simultaneously become a passionate proponent of expanding institutional practices. As a director she values acting that draws from breath, translucence, and stillness. Yet she finds short rehearsal periods and temporary relationships with professional performers inhospitable. To remedy this—and to give actors a more central place as devising partners in each production— Zizka has launched a new program to form a Wilma ensemble. Fourteen local actors are currently training and experimenting at her weekly atelier; it is, she says, “a constant journey” to help them locate “a thinking body” ready for rigor. These workshops are laying groundwork for future collaborations to be sustained over time: an ensemble structure that will allow the director to build upon each successive theatre project, rather than starting over again with a new group of actors each time.
Too many American theatres just try “to get better at the business of selling it, but we have to look at the conditions for the artists, who are freelancers,” says the director. Her innovations promise to make a more enduring and satisfying artistic home. “That’s what got me really excited about taking a new step,” she adds.
Immigrants, like artists, may always feel like outsiders. But this too serves as a point of inspiration. Zizka envisions a racially mixed group developing projects together, perhaps eclipsing national and ethnic backgrounds with a collective identity. “What I’m doing is to make the actor the center again, giving them the power to be present onstage and use their own imaginations. But also giving them tools to become better at what they are doing. I want to open up the territory and imagination of what acting and theater can be.”
Her future plans include shaping a major original theatre piece dealing with the recent global migration crises. Meanwhile, in a notoriously tough economic climate for the nonprofit performing arts, she’s fiercely proud that the theatre she founded more than 30 years ago still exists and experiments. “That art houses like the Wilma can survive is like a little miracle,” she says. “We are like a tiny raft navigating changing seas. We are still attracting audiences, and that is quite an achievement.”
The Vilcek Prize for Creative Promise in Biomedical Science
Fernando Camargo, Ph.D.
Scientific precocity might be Fernando Camargo’s defining quality. At the age of 38, Camargo, an associate professor at Harvard University and Boston Children’s Hospital, has peppered biomedical literature with unexpected findings that have upended long-held views and challenged conventional thinking. His work on the molecular controls of cell growth and the mechanism of blood cell production has vaulted him into a scientific vanguard whose efforts could advance cancer treatment and improve transplantation outcomes.
Watching his father grow onions and potatoes on their family farm near Arequipa, his hometown in southern Peru, Camargo developed an early interest in biology. His family, which includes several physicians, encouraged him to study medicine after high school. But after a year in medical school at Peru’s Catholic University of Saint Mary, he reckoned with his real calling. To Camargo, the prospect of uncovering the causes of disease and developing life-saving cures seemed more appealing than a career spent treating a few patients.
Hailing from a family of modest means in a country with few scientific resources, Camargo applied to dozens of universities in the United States for undergraduate studies. In 1997, thanks to a scholarship, he enrolled at the University of Arizona, Tucson, for a bachelor’s degree in biochemistry. Smitten with molecular biology, which increasingly claimed his interest, he spent months in the lab of molecular geneticist Robert Erickson. There, he performed gene therapy experiments in a mouse model of a rare genetic disorder of cholesterol metabolism called Niemann-Pick disease type C. “Nobody in my family had ventured outside of Peru. And here I was in the United States, working with genetically engineered mice,” Camargo wistfully recalls.
Camargo’s brush with stem cell biology happened at Baylor College of Medicine in Texas, where he began doctoral studies in 2000. His graduate advisor, Margaret Goodell, who became something of a lodestar to him, glimpsed in her protégé the glimmering mix of intellect and virtuosity common to promising scientists. In Goodell’s lab, Camargo examined an extraordinary claim that took the stem cell field by storm when it first appeared in the literature in the early 2000s. Unlike embryonic stem cells, which are developmental blank slates that can generate virtually all types of cells found in adult humans, adult stem cells are thought to possess limited potential to transform into cells found in their tissues of origin. But the eyebrow-raising reports claimed that adult stem cells sometimes behave like their embryonic counterparts, mimicking their trademark capacity to engender all types of cells—an ability dubbed pluripotency. Disproving the claim, Camargo’s work revealed that the seeming pluripotency of adult stem cells was in fact the result of their rare fusions with cells in adult tissues. The findings, published in Nature Medicine in 2003, brought clarity to a field roiled by controversial reports and propelled Camargo into a premier league of stem cell biologists.
The widely acclaimed work promptly earned him a prestigious fellowship at the Whitehead Institute for Biomedical Research in 2004. The Whitehead fellowship, a coveted honor bestowed on a vanishingly small number of promising young researchers, served as a crucible for Camargo’s talent. There, Camargo developed a path-breaking technique that vastly improved researchers’ ability to follow the fate of blood-forming stem cells.
In his Pulitzer Prize-winning book The Emperor of All Maladies, a sprawling account of the history of cancer that stretches across millennia to ancient Egypt, physician-writer Siddhartha Mukherjee says, “Every decade has a unique hematological riddle.” In Camargo’s time, that riddle may well have been the precise origin of the cells that course through blood. To study blood development, researchers typically purify blood stem cells from the bone marrow of mice and transplant them into mice exposed to radiation, thus creating a tractable experimental system. But these manipulations result in an artificial environment that hampers a genuine understanding of the physiology of blood development. Through a monumental effort, Camargo developed a genetic barcoding system to mark individual blood stem cells and their progeny in living mice, sidestepping transplantation and radiation. The barcode, which allows researchers to track virtually every circulating blood cell, led to a surprising insight.
Contrary to an entrenched view that blood stem cells generate most blood cells, Camargo found that the surprisingly long-lived descendants of blood stem cells, called progenitor cells, give rise to most cells in blood. Because progenitor cells are more abundant and long-lived than blood stem cells, the finding, published in Nature in 2014, might help improve cord blood transplantation in the clinic. “Enhancing the progenitors’ activity could potentially lead to higher rates of engraftment for blood transplant patients, making transplantation safer and more efficient,” explains Camargo.
Camargo’s studies also extend into cancer and regenerative medicine. Since the mid-2000s, he has focused on a signaling mechanism that serves as a gatekeeper for cell division and growth. He uncovered a protein called Yap1—a pivotal gene switch in a biochemical circuit called the Hippo pathway—that tamps down or ratchets up the division of cells in response to physiological needs. “Our work was crucial in proving that this pathway, which was first described in fruit flies, is functional in mammals,” he says.
Over the years, Camargo’s work has led to a wealth of insights. Notable among them: cells use a crowd-sensing mechanism, mediated by Yap1, to control organ size; Yap1 can either boost or stall the proliferation and activity of stem cells; and the Hippo pathway is a prime driver of cancer. “Many epithelial cancers—lung, liver, pancreatic—show high levels of Yap1. Excitingly, we have shown in mouse models that disrupting Yap1 blocks tumor growth,” he says. Bolstered by these findings, Camargo has partnered with drug companies to find compounds that can alter the activity of the Janus-like Yap1, blocking the protein for potential cancer treatment or boosting it for use in regenerative medicine. With can-do optimism, he adds, “My goal in the near future is to have a Yap1 inhibitor or activator ready to be tested in patients.”
If his early accomplishments are any indication, those goals might be well within his reach in the coming years. Camargo attributes his success to the many opportunities, mentorships, and partnerships that eased his scientific path in the United States. “The melting pot of the best and brightest minds has tremendously helped my career,” he says.
The Vilcek Prize for Creative Promise in Biomedical Science
Roberta Capp, M.D.
Roberta Capp has a grand vision. She hopes to make health care easily accessible to those in dire need of it. As assistant professor of emergency medicine at the University of Colorado, Denver, Capp is well-placed to tackle the widely recognized hurdles to health care delivery in the United States. But it is perhaps her own life experiences that have emboldened Capp to take on the daunting task of improving health care.
Capp’s journey from a hardscrabble childhood in the bustling state of Sao Paulo, Brazil, to the leafy quadrangles of the University of Colorado, Denver, is a testament to the triumph of willpower over circumstance. Raised by a single mother who eked out a living through fortune-telling and sundry jobs, Capp immigrated to the United States at the age of 14, faced with the formidable prospect of life in a foreign country whose language she did not speak. Before entering high school, Capp juggled a series of jobs to help support her mother and sister in Orlando, Florida, where the trio had arrived. At first, her newfound home, full of the financial hardships that faze fresh immigrants, seemed barely better than the country she had left behind. Yet her perseverance propelled her toward the future of her dreams, even as she graduated as high school valedictorian and her family slowly found its footing.
From a young age, Capp nursed a deep sense of vocation that shaped her career choice. “I knew that medicine was what I wanted to do,” she says. So she enrolled in premedical studies at the University of Colorado, Boulder, and moved to the city with her family in 1999. “We were like the three musketeers. We were all dependent on each other, so we all moved,” she recalls. At Boulder, she proved to be a standout in molecular and cell biology, having won more than a dozen scholarships that supported her studies, notable among which are a Coca-Cola scholarship, a Gates Millennium National Scholarship, and a Top 10 College Women in the United States prize, jointly bestowed by Glamour magazine and L’Oréal on young women with leadership potential.
Encouraged by a mentor at Denver who knew of her long-cherished ambition to become a surgeon, Capp applied and was accepted to Harvard Medical School in the fall of 2003. There, she found her true calling through a traumatic personal experience. While on a visit to Boston, Capp’s uninsured mother was diagnosed with ovarian cancer that had spread to her lymph nodes. Though the tumor was quickly removed at Brigham and Women’s Hospital, thanks to Capp’s professional acquaintances, the harrowing episode proved to be a compelling eye-opener on the continuing plight of the uninsured. Surgery quickly lost its initial tang, as Capp came to terms with the issues that bedevil health care quality and access in the United States. “My mom’s experience shaped my choice of specialty,” says Capp, who soon began a residency in emergency medicine at Harvard.
She pursued her choice with single-minded focus, completing a competitive two-year clinical research fellowship on health care policy at Yale University sponsored by the Robert Wood Johnson Foundation. During this time, through analysis of local and national databases as well as community-based research, she found that most patients with poor access to primary care frequently rely on emergency departments for conditions that might have been better treated or even avoided with timely intervention by primary care physicians. Analysis of national data sets revealed that Medicaid enrollees often use emergency departments for non-urgent conditions, largely because many primary care physicians turn down Medicaid. Further, her studies found that patients who suffer from complex and chronic conditions face a seemingly insuperable cavalcade of informational, logistical, and financial barriers to primary care. “They get the run-around and end up in the emergency department, which they know will be open 24/7,” says Capp.
To help remedy the difficulties of such patients, who place an outsize burden on overextended emergency care workers, Capp developed a program to identify such patients and pair them with trained professionals in their own communities. Dubbed navigators, these professionals help guide patients through often-labyrinthine primary care settings, from securing appointments to ensuring follow-ups. To evaluate the efficacy of navigators, she launched a yearlong randomized controlled trial and found that patient navigation services led to reduced emergency department use and hospital admissions—tantamount to a potential economy of more than a million dollars in health care costs. Further, a cross-sectional study of adult Medicaid enrollees in an urban setting revealed that almost half the enrollees preferred to consult a primary care physician rather than visit the emergency department for minor, non-urgent complaints if an appointment was immediately available. Together, these findings highlight the need to reexamine Medicaid policies to help redirect such patients to the primary care system, says Capp. To that end, she is working with Medicaid officials in Colorado to improve access to health care.
Capp’s efforts have also been focused on another aspect of emergency department overuse: bounce-back visits. Many patients return to emergency rooms with persistent symptoms within little more than a week after discharge. Because bounce-back visits can be a consequence of the natural course of disease, inadequately coordinated care, or outright medical errors, Capp developed a computer algorithm to scan such returns and identify those resulting from medical errors. With remarkable sensitivity, the algorithm revealed that such errors are often systemic, and Capp says that identifying them can help curb return visits.
Thanks to the support of her longstanding mentor Richard Zane, chair of the emergency medicine department at the University of Colorado, Denver, Capp’s contributions to health care coordination earned her an assistant professorship in the medical school at Denver, where she returned in 2013 to her family’s delight. Over the coming years, Capp hopes to make health care patient-centered and to reduce its cost and improve its quality. “Someday, I would love to be the medical director for Medicaid nationwide and drive policy decisions with my research experience. The beautiful thing about this country is that if you are passionate and persistent, you can achieve your dreams,” she says.
The Vilcek Prize for Creative Promise in Biomedical Science
Houra Merrikh, Ph.D.
Every great story needs a gripping conflict. Few researchers appreciate this maxim better than Houra Merrikh, who has swiftly risen to scientific prominence for uncovering hidden conflicts between the machinery that copies DNA in living cells and the one that transcribes its genetic code. Merrikh, an assistant professor of microbiology at the University of Washington, Seattle, ascribes her early success to unbridled curiosity and childlike impatience. Yet the singular trait that enabled her to illuminate the mechanics of life itself might be her tireless spirit.
The story of Merrikh’s early years is at once a grim reminder of the grueling choices that many immigrants face and a hopeful message for those mired in modest circumstances. Merrikh was raised amid the turmoil of war-torn Tehran in the 1980s by educated parents who held lucrative jobs in the Iranian capital. Fleeing the mandatory draft looming before her brother, the family moved to Turkey when Merrikh was 3 years old. With the help of a family member who lived in the United States, they applied for green cards, which they hoped would be passkeys to a better life.
But the interminable wait—a frustrating 13 years—was punctuated by financial hardships, her mother’s mental illness, and her parents’ divorce. At 16, with a bit of help from benevolent strangers who have since become friends, Merrikh immigrated to Texas, leaving her own family behind. To put herself through community college, she waited tables, sold cars, and tutored students. And in 1999 she enrolled at the University of Houston, Texas, for a bachelor’s degree in biophysics and biochemistry.
While at Houston, Merrikh became enamored with basic research in biochemistry, which she pursued for her undergraduate honors thesis. After graduation, she moved to Boston University to work as a technician in a plant genetics lab. Steeping herself in scientific literature, she enrolled in a doctoral degree in biochemistry and molecular biology at Brandeis University in 2003. After a brief stint in the lab of molecular biologist Michael Rosbash, Merrikh hit her stride with biochemist Susan Lovett, who studies how bacteria weather attacks on their DNA. “She was a great female role model who always kept science exciting,” says Merrikh.
At Brandeis, Merrikh embraced the tools of molecular biology to unearth a then-novel mechanism by which bacterial cells respond to assaults on DNA. She discovered that DNA damage triggers a cascade of events—mediated by proteins called IraD and RpoS—that helps actively dividing cells survive onslaughts on DNA. Complementing a canonical route for DNA repair, the new mechanism, published in Proceedings of the National Academy of Sciences in 2009, expanded the ways in which cells cope with damaged DNA. “In the two years I spent in [Lovett’s] lab, I had two publications and my first child,” recalls Merrikh.
Building on the success of those early efforts, Merrikh pursued a postdoctoral apprenticeship in the lab of Massachusetts Institute of Technology molecular biologist Alan Grossman, widely recognized for his work on DNA replication in bacteria. “You can’t think about DNA damage and repair without understanding DNA replication,” says Merrikh. In Grossman’s lab, she explored how bacteria time DNA replication, ensuring that the genome is promptly copied no more than once per cell cycle. She studied a previously uncharacterized protein called YabA, which controls the binding of bacterial DNA to a protein called DnaA, whose essential role in kick-starting DNA replication had long been known. The discovery of the mode of action of YabA unveiled a novel mechanism by which bacteria choreograph the copying of their genome. Because untimely DNA replication can lead to unchecked cell division, these findings are crucial to a molecular understanding of cancer, a condition marked by runaway DNA replication.
Galvanized by those findings, Merrikh continued to tease apart the mechanics of DNA replication in Grossman’s lab. To survive, all cells must replicate their genomes and express their genes. However, these two life-sustaining processes, which often unfold simultaneously on the strands of DNA, pose a spatial quandary: The cellular machinery that replicates DNA and the one that transcribes genes can collide head-on, destabilizing the genome with disastrous consequences. To minimize the risk of such conflict, nature has niftily co-oriented many essential and highly expressed genes with regard to DNA replication. “So the two machines move in the same direction,” says Merrikh.
Researchers had long believed that such co-orientation of genes was a perfect solution to the potential conflict between replication and transcription. Merrikh’s work surprisingly revealed that conflicts can occur even when genes are co-oriented in this manner. Because DNA replication in bacteria is around ten- to twentyfold faster than transcription, the replication machinery can effectively rear-end the transcription apparatus, throwing both processes out of kilter. “This work showed that conflicts are a universal problem for all genes on the chromosome,” says Merrikh. The findings, published in Nature in 2011, signaled her arrival on the molecular biology stage. The same year, she accepted an assistant professorship at the University of Washington, Seattle.
In Seattle, Merrikh pursued the question of the conflict, ultimately finding that gene orientation can accelerate evolution. She wondered why some genes, despite being essential for survival, are not co-oriented with DNA replication. Her work revealed that such genes, which face a heightened risk of head-on collisions, are subject to increased mutation rates. The attendant mutations, it turns out, help speed evolution in a highly orchestrated manner. The findings, published in Nature in 2013, established head-on conflicts as a long-elusive mechanism to target mutations toward particular genes in the genome. “This mechanism may drive the development of antibiotic resistance in bacteria and cancer in human cells,” she explains, hinting at the work’s potential medical implications. Before long, Merrikh’s team laid bare the precise mechanism by which head-on conflicts boost mutation rates in bacteria.
Over the coming years, Merrikh hopes to delve deeper into the mechanics of DNA replication by visualizing the bump and grind of individual molecules in cells through biophysical methods. She also hopes to determine whether the effects of conflict-driven mutations on disease can be systematically predicted. “I don’t know if this will take five or fifty years, but the ultimate goal is to take the basic knowledge and apply it to medical issues,” she says.
The Vilcek Prize for Creative Promise in Theatre
Sarah Benson grew up in a small village in England, watching her father create his own tools as he built parts for the manufacture of ships. “Everything was imagined from the ground up,” she says. “He instilled in me a belief that you can make anything with your hands if you apply enough ingenuity and care.”
Invention and persistence have served Benson well in her journey to success as artistic director of Soho Rep, a New York theatre consistently lauded for its innovations. Following her father’s talents, she became interested in engineering and math and won a scholarship to attend a high school far from home; the school’s theatre activities offered camaraderie and opportunities to devise solutions with each play. She was hooked. Benson scoured local libraries and secondhand bookshops for published plays of all kinds, finding inspiration for stagings in her reading. The director has been a voracious reader ever since, continuing her studies with an undergraduate degree at Kings College in London before landing a 2002 Fulbright scholarship to pursue a master of fine arts degree at Brooklyn College. These applied studies in directing, under her mentor Tom Bullard, gave her an opportunity to learn how to work with actors—a skill that can be acquired only through experience. Opting for a third year of training and a visa extension, Benson used a Brooklyn College fellowship to start an internship at Soho Rep, then helmed by artistic director Daniel Aukin. Known for its commitment to adventurous new plays with an experimental bent, the small but scrappy company needed all hands on deck. Aukin soon asked his capable protégé to run the company’s developmental director’s lab.
Other artistic opportunities arose as Benson found community in New York’s lively progressive theatre scene. In 2005 she was invited to curate the Prelude festival, an annual autumn presentation of works in progress set to premiere later in the theatre season; drawing on her passion for new writing, she chose to highlight plays from a rising generation of dramatists. It was a success, and it helped Benson to establish a reputation in the close-knit downtown theatre community. By then, she was thoroughly ensconced in the American theatre, which she found she preferred to the British stage. “It’s a more visual culture,” she reflects, adding that she found it “liberating not to make work in a literary context.” Still, she says, making it as a freelance director in New York was an economic challenge: “It was definitely rough at times.”
Her programming at Prelude and other venues, along with her leadership at Soho Rep, led to her appointment as the company’s new artistic director in 2006 when Aukin departed. For her first major staging, Benson chose to stage Blasted, a legendary 1996 drama by the late British playwright Sarah Kane. The play depicts political violence and rape in a startling apocalyptic scenario rooted in contemporary conflicts. Kane’s abstract and lyrical writing had inspired a wave of theatre-makers throughout the world prior to the author’s suicide in 1999; in the U.S., however, Kane’s disturbing oeuvre was mostly read rather than staged for production. “I literally had no idea what was going to happen,” says the director. It was a bold choice for her debut as artistic director, coinciding with the 2008 financial crisis.
As with all of her projects, Benson saw the staging as an opportunity for discovery. “I am attuned to situations and people I encounter that shift how I feel—things that I find baffling, embarrassing, bizarre, or frightening are often the most valuable,” says the artist. Seeking inspiration for Blasted, she visited waste sites on Staten Island, spoke with mental health professionals, read T.S. Eliot’s poem “The Wasteland,” and researched the wars in the Balkans.
At Soho Rep, Benson found opportunities to make a production’s design central to interpretations of a play. She formed ongoing collaborations with young artists such as set designer Mimi Lien, exploring the use of the theatre as a civic space. Benson says she likes to take the entirety of Soho Rep’s small, flexible playing area into consideration—not just to conceive a boxy unit onstage. “I want to constantly remind myself and the audience of the act of theatre—one that involves us all showing up in person and together creating the experience.”
That commitment can be seen in projects Benson produces as artistic director, as well as in those she directs herself. For Generations, a play by the British dramatist Debbie Tucker Green commemorating South Africa’s AIDS fatalities, directed by Leah C. Gardiner, Soho Rep spectators sat around a modest township kitchen hearth. Pots boiled on the stove. Audience members also discovered that a choir had been dispersed among them when they stood up to sing and mourn. With this calculated mise-en-scène, the privacy of home and hearth transformed into a public sphere, with reverberations in both directions. (The New York Times named the production one of the best of 2014, and in 2015 the Village Voice named Soho Rep the best theatre company in New York.)
Benson’s tour de force, however, came with her own staging of An Octoroon, a contemporary reimagining of Dion Boucicault’s 1859 melodrama by Branden Jacobs-Jenkins. Boucicault’s original 19th-century drama—hinging on the fate of a young woman who discovers she has mixed blood and thus may be enslaved—had been one of the historical works Benson devoured as a student. Jacobs-Jenkins’s highly ironic version emphasized the troubling racial caricatures in the canonical play, simultaneously raising questions about how America fabricates narratives about race. It made for a directorial challenge: wild in its energies, but calling for careful calibration of its sensitive themes. Her approach made bold use of minstrel forms, including redface, whiteface, and blackface worn by actors of different ethnicities. Benson says she wanted the audience “to constantly question what they were seeing on stage and rupture how people were being categorized.” The provocative production, which also featured a life-size rabbit and an abundance of humor, won the 2014 Obie Award for Best New American Play and enjoyed a transfer presentation at Theatre for a New Audience in 2015.
For the moment, Benson is busy juggling new projects while running the company. She prefers not to speculate about the future. But her trajectory is clear: Like her father, she is a resourceful builder, and the American theatre is benefitting from her skilled craft.
The Vilcek Prize for Creative Promise in Theatre
Freelance director Desdemona Chiang was born in Taipei, Taiwan, and immigrated to the United States when she was just 3 years old. She spoke Mandarin, her first language, in the care of her grandmother while her parents were away in the U.S. pursuing their graduate studies. After Chiang joined them in Southern California—part of a wave of Asian immigration to the region in the 1980s and ’90s—she started elementary school in an English as a Second Language program. Separated from the other kids for part of each day, she felt keenly aware of her immigrant family’s differences. The wonders, fears, and estrangements of that immigrant upbringing in Los Angeles and Orange County have always nourished her artistic sensibilities. “I love confronting worlds that are not my own,” says the artist, “investigating stories and territories that are marginalized and underrepresented.”
Given Chiang’s dramatic first name (referencing the wronged heroine in Shakespeare’s Othello), people sometimes wonder if her life in the theatre was inevitable. But in fact, she intended to major in molecular cell biology at the University of California, Berkeley, when, as a freshman, she enrolled in “Introduction to Acting” to fulfill a distribution requirement. (“I figured it was an easy A,” she says with a laugh.) Instead she found herself swept away, awed by the theatre’s potential to express powerful forces she had always reckoned with in her life and mind—otherness, disorder, death, ritual.
Hungry to master the art form’s intricacies, Chiang would sit in the university’s dark auditoriums for hours watching her peers’ technical rehearsals, when a production’s collaborators build its physical life moment by moment, lighting cue by lighting cue. A directing class crystallized her interest; directing offered her a role filled with the analysis and problem-solving at which she excelled, yet it allowed her to be intensely creative and generative. A double major was born, and graduate training followed, leading her to Seattle for a master of fine arts in directing at the University of Washington (UW).
After graduating, she cut her teeth staging new plays, working with Berkeley’s Impact Theatre to develop and direct work with emerging writers. She also applied her knack for dramaturgy—the literary and artistic advising of plays and productions—at area organizations such as San Francisco’s Playwrights Foundation, Crowded Fire Theatre Company, and Magic Theatre. “When you first come out of school, you do whatever you are hired to do,” she says of the five years she spent honing her craft, trying to realize each playwright’s distinctive voice. It was not always easy. “Being an Asian female director in America is hard,” she says. “There is no social validation or model for it. Asian cultures tend to reject the notion of a career artist.”
Various mentors helped her learn how to approach scripts in development. UW professor Jon Jory, formerly producing artistic director of Actors Theatre of Louisville and a longtime champion of new American playwriting, “imprinted the way I work and think,” Chiang says. Encouraged, she turned to bold tactics to realize the unusual visions of playwrights. One example of her creative innovation: For The Hundred Flowers Project, Christopher Chen’s play about a group of Asian-American actors struggling to make a drama about Chairman Mao Tse-tung, she synthesized sound, text, mechanized choreography, and video. The director needed to evoke a journey into madness, as China’s Cultural Revolution collided with today’s America and the unmoored realities of the internet. She decided to experiment in a series of technology workshops; the actors used their live bodies in relation to live video feeds and even iPhone cameras. From those experiences, she found a way to evoke what she terms a “chaotic cyberworld”—the ultimate representation of her own “amalgamated ethos” as a Chinese immigrant, American citizen, and member of the internet generation.
Along the way, Chiang found institutional recognition: She was a directing fellow at Oregon Shakespeare Festival (OSF) and with the Drama League in New York, as well as a member of the Lincoln Center Theater Director’s Lab. She has also tackled classics such as Measure for Measure, which she mounted for Seattle Shakespeare Company. (She is scheduled to direct The Winter’s Tale at OSF in June 2016.)
But her work took a quantum leap when she co-founded Azeotrope, a Seattle-based company, in 2010. With a mission to produce new and contemporary stage productions about the invisible and marginalized, the theatre occupies a progressive place on the aesthetic and political spectrum. As the resident director, co-producer, and key lead artist, Chiang could now seize the creative initiatives, imagining new projects from scratch and determining nearly every element, from what space to perform in to what text and style. (Freelance directors working from commission to commission rarely have these possibilities, which tend to come with a regular platform for their ideas.)
Azeotrope has staged regional premieres of dramas by nationally known writers such as Stephen Adly Guirgis, Rajiv Joseph, and Adam Rapp. But with the company’s most recent project, Sound, by Don Nguyen (coproduced with ACT Theatre this fall), the director has been able to own another level of commitment. Sound depicts a controversy in the Deaf community; Chiang staged it half in American Sign Language (ASL) and half in English—a choice that alters the audience’s consciousness while underscoring themes about a marginalized group’s struggles.
While she envisions Azeotrope as a future pathway, Chiang has other aspirations too. “I would love to work more in New York City,” she says quickly. “I’m also interested in stretching into other genres or media—perhaps opera, musicals, or even film.” A natural leader, the young director seems like a strong candidate eventually to run one of America’s large resident theatres, at a time when national organizations have been rethinking their priorities and constituencies. “What I strive for in my work is a fight for visibility, representation, and agency,” she says, “and I hope my career can be an example to future Asian artists who wish to make a life in the American theatre.”
The Vilcek Prize for Creative Promise in Theatre
Yi Zhao’s paternal grandmother was a painter, but no one else in his family showed signs of an artistic bent. So Zhao, born in Beijing, China, in 1986, always assumed that a career in mathematics or computer science awaited him after finishing school. But a few coincidences led him to detour into the arts. For one thing, he spent part of his childhood in France, where his mother worked for the United Nations, so he had an uncommon sense of cultural openness for a teenager. Although he knew no one in the U.S., the 17-year-old ventured to the University of Chicago for an American liberal arts education, arriving in 2003 to pursue a bachelor’s degree. He hadn’t thought much about the performing arts. In fact, he says with a laugh, “I honestly had never even seen a play before I designed one.” But he fell in love with theatre through sheer happenstance.
One day while wandering the campus, he chanced upon a theatre group’s rehearsals. The troupe invited Zhao to stay; they became friends, and soon he found himself hooked on the technical side of staging productions—programming the lights on the computer fascinated him. He learned the ropes of electrics and stage spaces, and his creative satisfaction grew with each project. While working on student productions in the evenings, he studied fine arts—training formally in photography, and developing film in a darkroom, the analog way.
After college, like many of his creative peers without firm plans, Zhao moved to New York City, where he worked for a commercial photographers’ agency with clients advertising everything from cars to cosmetics. “That wasn’t for me,” he says tactfully. But he knew he enjoyed being around artists. To keep his theatre interest going, he started doing technical work at Performance Space 122, the legendary East Village arts center, which meant a workweek of 70 to 80 hours for almost two years. Zhao was designing lighting for visiting artists from around the world and found the social connections thrilling, but it wasn’t sustainable. His post-graduation American work visa put onerous restrictions on any freelance work—an essential pathway to working in the arts. Worse, it was due to expire. To buy time while he figured out his career path in a profession notoriously tough to crack, Zhao decided to apply to a variety of graduate schools.
Another coincidence led him to the Yale School of Drama. Zhao was on his way up the Eastern Seaboard to interview for a master’s program in graphic design at the Rhode Island School of Design (RISD) when he stopped in New Haven, Connecticut, to visit a friend at Yale’s prestigious conservatory. He decided the drama school made an ideal work environment and training ground, and met the lighting designer Jennifer Tipton, a professor in the school’s design department. Tipton not only accepted him into Yale’s three-year intensive master of fine arts program, but she also mentored him in every aspect of the discipline. Zhao thrived under her tutelage (he also cites the photographer Laura Letinsky as an artistic guide), enjoying a systematic approach to training as a lighting designer after years of trial and error on his own. “Yale’s holistic approach was right for me,” he says, noting that the school also provided generous financial aid. Apprenticing with the internationally renowned Tipton gave Zhao a structure, a philosophy, and “an inherent coherence” as a theatre artist—what he had been seeking since his undergraduate days.
That foundation served him well after graduate school. He has garnered acclaim for his thoughtful and subtle designs serving a wide variety of theatre productions and aesthetics. He names many influences on his work—stage director Robert Wilson for his “symbolic use of color and composition” and photographer Philip-Lorca diCorcia for making “artificial light to create an expressionistic, painterly sense of drama in the most quotidian settings.” The young designer says he doesn’t think he has a discernible “style” since a good designer responds to the needs of his collaborators—the director, set and costume designers, and the playwright—making it a less tangible medium than some other professions in theatre. Whatever the aesthetic, Zhao has proven a key collaborator for some of the most ambitious U.S. productions in recent seasons. Among the highlights are an innovative 2014 staging of Plato’s Republic by the young company Hoi Polloi at JACK, a Brooklyn art center. For that project, Zhao worked with set designer Mimi Lien to devise dimmable, remote-controlled glowing columns that the actors could move around the white space—a metaphor, the designer says, for “the elegance and fallacy of intellectual inquiry, and the building and collapse of a city.”
He has collaborated extensively with director Lileana Blain-Cruz (a Yale classmate) on productions including the world premiere of War, a new play by Brandon Jacobs-Jenkins at Yale Repertory Theatre, for which he evoked the thoughts of a comatose woman using a tight follow spot. For Blain-Cruz’s 2015 production of Shakespeare’s Much Ado About Nothing at the Oregon Shakespeare Festival, his lighting expressed a different character’s perspective in each scene, which he describes as “complete and shocking shifts in mood throughout the piece.” For a production of Hamlet at Philadelphia’s Wilma Theater (directed by Vilcek Prize recipient Blanka Zizka), he combined beams of golden light and thick haze to conjure the corruption of the Danish court.
With these accomplishments under his belt, and growing national recognition for his work, Zhao is already thinking about the future. “I definitely want to do big opera houses,” he says quickly when asked; in particular he dreams of the summer music festivals, where designers can realize large-scale productions in beautiful outdoor settings. He aspires to work in Europe’s large state theatres, which devote salaried acting ensembles and enviable design budgets to the classical repertory he loves. But, Zhao confesses, his heart remains in New York’s off-off-Broadway scene and with artists trying something new on any scale. “I love a good small theatre,” he says unabashedly. “I love a good political play. It can change lives.”
The Vilcek Prizewinners each have a unique story to tell. Watch interviews with the awardees on our 2016 Vilcek Prizes YouTube playlist.
Vilcek Prizes Gala
Browse photos and video clips from the Vilcek Foundation Awards Gala, honoring the recipients of the 2016 Vilcek Prizes.