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Focus Summer 2019

W I S TA R S C I E N C E : B O L D. I M A G I N AT I V E . I N S P I R E D.

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T H E

W I S TA R

I N S T I T U T E

B E YO N D VA C C I N E S :

Looking to Cures for Infectious Diseases

The Antibiotics Crisis

News from the Institute

Beyond the Lab

Symposium Recap


COVER STORY

Beyond Vaccines: Looking to Cures for Infectious Diseases While vaccines are considered the single most important health achievement in history, there is a mandate to stem the global threat of HIV/AIDS, headlines predict mosquito-borne diseases will infect half the globe, and many new disease catastrophes are popping up. Wistar scientists are putting their research “eggs” into two baskets: new vaccines and immune therapeutics.

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ew infectious diseases are on the rise: In 2015 and 2016, there was an upswing in Zika outbreaks in the U.S., and the virus still impacts many parts of the world. The Ebola epidemic in the Democratic Republic of Congo (DRC) is the second largest in history, according to the Centers for Disease Control and Prevention, and HIV remains an incurable disease. All of these epidemics beg one question that members of Wistar’s Vaccine & Immunotherapy Center are interested in solving: Can we create a cure for infectious diseases? In particular, Kar Muthumani, Ph.D., assistant professor in the Vaccine & Immunotherapy Center and director of the Laboratory of Emerging Infectious Diseases, is pursuing whether we can develop antibody therapeutics to help people recover from infection. “Historically, vaccines have been our answer to global disease prevention but look at Ebola in the DRC — when an outbreak has already started, people with the disease need a therapeutic not a

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preventative answer,” said Muthumani. “In my lab at Wistar, we are focused on therapeutics that could be given to anyone who comes down with symptoms. Patients would receive a blood test to confirm the type of disease and take the therapy for that specific disease.” Muthumani’s expertise is in design and creation of synthetic DNA-based vaccines and therapeutics. His work crosses over between infectious diseases and cancers. He’s actively working on Zika virus, Mayaro virus, chikungunya virus, Middle East respiratory syndrome (MERS), Nipah virus, Junín virus, Crimean-Congo hemorrhagic fever, dengue virus, and HIV. Muthumani is strongly committed to antibody therapy as a strategy to provide relief for emerging disease situations. Antibody therapy is a form of immunotherapy that uses monoclonal antibodies (mAb) to bind to specific cells or proteins and stimulate an individual’s immune system to fight infection. He is currently working with partners to characterize immune cells and antibodies

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In my lab at Wistar we are focused on therapeutics that could be given to anyone who comes down with symptoms. Patients would receive a blood test to confirm the type of disease and take the therapy for that specific disease. —KAR MUTHUMANI, PH.D.


from survivors of South India’s 2018 Nipah outbreak in Kerala, with the goal of engineering these antibodies leveraging the synthetic DNA technology, and delivering them directly to patients. These antibody therapies would be ready to attack the virus and boost the body’s defenses. The goal is to provide an immediate protection while the body builds a long-lasting immune response to traditional immunization. Just two floors away at Wistar is the lab of Luis J. Montaner, D.V.M., D.Phil., director of the HIV-1 Immunopathogenesis Laboratory and HIV Program leader, who is also focused on a cure, but for another infectious disease — HIV/AIDS. There are approximately 37 million people living with HIV worldwide and 21.7 million are receiving antiretroviral therapy (ART), according to the World Health Organization. ART suppresses the HIV virus and reduces disease progression, helping people with HIV live longer and preventing onward transmission. However, ART does not eliminate infection and has to be taken daily for life, thus the priority to move HIV cure research forward. Montaner’s 20+ years of HIV/AIDS research at Wistar has propelled him into his largest research project: the BEAT-HIV Delaney Collaboratory. He oversees a consortium of more than 80 top researchers from academia, government, nonprofit, and industry working to define the most effective way to combine immu-

Summer 2019

Illustration of Zika virus

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Together, we’re building on our teams’ extensive and established efforts to move forward and make those next transformative steps that will bring us closer to an HIV cure within our lifetime. —LUIS J. MONTANER, D.V.M., D.Phil.

The BEAT-HIV Collaboratory benefits from decades-long partnerships in the Philadelphia HIV community, including Philadelphia FIGHT, an organization that provides primary care and access to clinical research in HIV, and supports education, advocacy and outreach to people living with HIV and those who are at high risk.

BEAT-HIV.org

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notherapy regimens to advance new cure-directed efforts against HIV through new preclinical research and clinical trials. Their work centers on investigating where HIV hides after therapy and testing novel clinical strategies ultimately aimed at a cure that eliminates the hidden virus. The consortium has three important goals, including two first-inclass clinical HIV cure-directed studies: 1) Identifying where and how HIV hides in the body of people on antiretroviral therapy to better determine new strategies to kill the virus; 2) Stimulating the innate immune system to be stronger against HIV, combining a medication called pegylated interferon alpha 2b, which may help control viruses, and potent antibodies that can neutralize HIV; and 3) Introducing new “killer T cells” by bringing together two prom-

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ising gene therapy strategies, independently tested in humans, with the goal of engineering, growing and administering killer T cells that are uniquely empowered to find and kill HIV-infected cells. “Lifelong stigma, economic burden on society, strain on healthcare resources, and sheer toll on human life across the globe makes finding a cure a top priority,” said Montaner. “Together, we’re building on our teams’ extensive and established efforts to move forward and make those next transformative steps that will bring us closer to an HIV cure within our lifetime.” Wistar scientists are dedicated to the design and creation of vaccines and therapies to stem the tide of the global burden of disease. Research is one major piece of an integrated push across communities, governments and countries for the best global health outcomes. ■


BREAKING DOWN THE SCIENCE

The Antibiotics Crisis Resurgence of Old Bacterial Infections and New Research to Curb Them

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onsidered the quintessential medical revolution of the 20th century, antibiotics turned deadly bacterial infections into curable diseases and transformed medicine and surgery. Yet, 80 years after the discovery of penicillin — which saved millions of lives — antibiotics as we know them are not the cheap and effective “wonder drugs” they used to be, due to emergence of antibiotic or antimicrobial resistance (AMR). Some diseases that we considered long gone or easy to treat are coming back from the past, returning as serious public health threats. A 2014 Global Health Organization surveillance report stated we have entered the “post-antibiotic era,” in which common infections and minor injuries can kill again and the success of surgery, organ transplantations and cancer chemotherapy could be compromised. AMR: How It Happens and How It Spreads

Antibiotics kill bacteria by disrupting functions that are essential for their survival. AMR arises when bacteria develop the ability to defeat antibiotics that were once able to kill them. Just like any living organisms, bacteria evolve over time and some acquire resistance to stressful conditions in their environment, including

antimicrobial drugs. Bacteria that naturally evade the host immune system have a further survival advantage and are more likely to develop AMR faster. They rapidly outnumber the wild type bacteria. Additionally, genes that confer drug resistance can transfer from one species of bacteria to another and rapidly spread. While evolution is natural, human behavior has amplified bacterial resistance to antibiotics. Antibiotic use creates a selective pressure for resistant organisms, as sensitive ones are killed and those that survive have less competition in the environment. Therefore, AMR is enhanced by excessive or inappropriate use of antibiotics, such as: • Patients self-medicating with antibiotics to treat conditions that are not caused by bacteria (for example the flu or other viral infections); • Healthcare providers overprescribing antibiotics “just-in-case” or prescribing broad-spectrum drugs instead of more specific ones; • Excessive agricultural use that causes transfer of resistant bacteria from farm animals to people and affects the good bacteria present in the environment.

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We face a very pressing situation. A U.K. public health study predicts that by 2050, 10 million people will die every year because of antibioticresistant infections. —FAROKH DOTIWALA, M.B.B.S., Ph.D.

Dr. Dotiwala supervising a member of his lab.

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The AMR crisis is worsened by the lack of new antibiotic development by the pharmaceutical industry — in the decade between 2000 and 2010 only five new antibiotics have been approved for clinical use and AMR bacteria have emerged against these new antibiotics as well1. Several strains of resistant bacteria have been isolated so far, such as drug-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumanii, Enterobacteriaceae, Gonococcus and methicillinresistant Staphylococcus aureus (MRSA). Strains of Mycobacterium tuberculosis have become resistant to 10 to 20 antibiotics used in different regimens to treat them and MRSA has now developed resistance to vancomycin, an antibiotic specifically used to treat it. “We face a very pressing situation,” said Farokh Dotiwala, M.B.B.S., Ph.D., assistant professor in Wistar’s Vaccine & Immunotherapy Center. “A U.K. public health study predicts that by 2050, 10 million people will die every year because of antibiotic-resistant infections, such as gram-negative bacteria, tuberculosis and malaria2. The cost associated with AMR will run into 80 trillion dollars per year.” AMR infections frequently occur in hospitals. The Centers for Disease Control estimated that they account for approximately 1.7 million infections and 99,000 deaths each year in the U.S. alone.


AMR represents an important economic burden to the health care system and to patients. When first-line and then second-line antibiotic treatments fail, doctors have to use more expensive drugs that have worse side effects, while patients with resistant infections tend to require longer hospital stays. In 2006, hospital-acquired sepsis and pneumonia cost the U.S. health care system more than $8 billion. In response to the worsening antibiotic resistance crisis, the pharmaceutical industry has begun to revamp its antibiotic discovery and development programs and the number of new molecules in the pipeline has been on the rise since 2014.3 Wistar is Contributing Important Research for the Development of Novel Antimicrobial Strategies

Dotiwala and his lab are developing a novel antibiotic strategy to combat AMR. This approach targets an essential pathway in bacteria, called isoprenoid synthesis pathway, and activates killer immune cells at the site of infection in order to destroy the bacteria that acquire

According to the World Health Organization, 490,000 people developed multidrug resistant tuberculosis globally in 2016.

resistance to antibiotics. Using computer-aided molecular modeling, the Dotiwala lab has evaluated millions of commercially available compounds for their ability to specifically target the isoprenoid synthesis pathway. The best hits have been validated and further studied with the goal of finding select compounds to move forward to clinical trials. The team is also taking an innovative approach to developing non-traditional antibiotics by “copying” natural antibacterial molecules used by our immune system. During his postdoctoral training, Dotiwala discovered a process that was named microptosis, through which killer immune cells — T lymphocytes and natural killer (NK) cells, attack and kill intracellular bacteria and parasites during an infection. Intracellular parasites grow and reproduce inside the cells of a host. As a defense mechanism, T cells and NK cells destroy infected cells by poking holes in their membranes and delivering toxic proteins that break down the cellular structures. What Dotiwala found is that killer cells can also use a similar mechanism to kill microbes themselves. At Wistar, the Dotiwala lab is further studying proteins used by killer immune cells in this process, with the goal of repurposing these substances as novel therapies for drug-resistant bacterial infections. “Such an approach is expected to be very specific and not cause major side effects, because we would be using weapons that are naturally part of our immune system’s arsenal to fight microbes,” said Dotiwala. “Importantly, due to simultaneous targeting of multiple essential bacterial systems by microptosis, the bacteria would not be able to develop resistance to this type of treatment, and this would be a critical advantage over traditional antibiotics.” While this and other research to create new medicines against AMR bacteria come to fruition for patients, we need to make prudent use of the “old” classes of antibiotics that are still effective. ■

Sources: 1. Antibiotic resistance threats in the United States, 2013. April 2013. Centers for Disease Control and Prevention Office of Infectious Disease. 2. Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations. Dec. 2014. O’Neill J., Review on Antimicrobial Resistance. 3. Targeting innovation in antibiotic drug discovery and development: The Need for a One Health—One Europe—One World Framework, 2016. Renwick M.J., Simpkin V. and Mossialos E. Appendix 1, page 83

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NEWS FROM THE INSTITUTE

Wistar’s Cancer Center Earns ‘Exceptional’ Rating and Receives $13.6M in Research and Education Grants from the NCI What This Means for the Nation’s Cancer Research Efforts

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istar has received an “exceptional” rating for the second review cycle in a row and renewed its National Cancer Institute (NCI) Cancer Center designation, retaining the title “NCI-designated Cancer Center” since 1972. It is proud to have built and sustained a program of excellence in cancer research for almost 50 years. But what does that mean? In fact, quite a lot. Across the nation, there are only 70 cancer centers that show the level of distinction deserving of NCI recognition and Wistar is one of them. The Institute, home to 31 laboratories that focus on groundbreaking science, is part of an even smaller elite group of seven NCI-designated basic cancer research centers in the U.S. From its collaborative, rigorous research programs, to its innovations in state-of-the-art technological facilities and its research depth through principal investigators at the nexus of innovation and exploration in cancer research, Wistar contributes major new discoveries that are the bedrock of the nation’s cancer research efforts.

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Wistar is not part of a healthcare system. It is not affiliated with a hospital, nor does it treat patients. Instead, Wistar scientists carry out basic scientific research that is the foundation of discoveries that could become future therapeutics and diagnostics. Recently, the NCI renewed Wistar’s Cancer Center designation, and the Institute received federal grant funding in the form of a Cancer Center Support Grant (CCSG) for $13.6 million over the next five years. This grant will continue to support Wistar’s competitive, world-class research programs and its shared facilities. It also positions the Institute to attract world-leading scientists studying the initiation, prevention and treatment of challenging cancers. ■

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NCI

After extensive peer review, the application submitted by The Wistar Institute’s Cancer Center for renewal of its Cancer Center Support Grant (CCSG) received an “exceptional” rating from the NCI for the second review cycle in a row. This achievement denotes Wistar’s prestigious standing among the nation’s best, a status gained and maintained through top research programs, historic partnerships, state-of-the-art core facilities, impactful educational programs, and scientific leadership. Designated Cancer Center

Learn more: cancer.gov/research/ nci-role/cancer-centers


BEYOND THE LAB

Dr. Kazuko Nishikura: the RNA Explorer Nishikura has been a pillar of Wistar science for the past 37 years. Her career overlapped with the rise and expansion of the RNA biology field, which explores the alternative functions of RNA in the cell, besides carrying the genetic information from DNA to proteins. Her foray into research happened at a time when scientists were only beginning to understand the function of RNA and its molecular mechanisms; she would end up contributing fundamental knowledge to the field.

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ishikura discovered the process of RNA editing, an important mechanism of genetic regulation. Her scientific journey has taken her on to explore several aspects and functions of RNA editing and its interplay with other molecular pathways.

Training with great minds of the time was the fertile scientific soil of her education as a scientist. Nishikura absorbed their intellectual curiosity. “I consider myself very lucky for having had a chance to observe in person how those big scientists addressed important biological questions,” she said.

Passion for Science Sparks

Born and educated in Japan and encouraged by her high school science teacher who recognized her scientific talent, Nishikura obtained her Ph.D. at Osaka University. She then pursued postdoctoral training at the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge, England, and Stanford University, two birthplaces of molecular biology. Photos of those times hang in her office, memories of a cherished past, and portray some very famous scientists who left their mark in history and in Nishikura’s career: Nobel Prize winners Max Perutz, Ph.D., who discovered the structure of hemoglobin and was her doctoral thesis advisor, and John Gurdon, Ph.D., whose work on reprogramming mature cells to stem cells laid the foundation for major advances in cloning and stem cell research. Nishikura spent two very formative years in his lab in Cambridge as a postdoctoral fellow, before moving to Stanford to work with another outstanding mentor, Roger Kornberg, Ph.D., also a Nobel laureate, who described how genetic information is passed from DNA to RNA.

An Expanding Field of RNA Biology

RNA biology became Nishikura’s main research interest, which she has continued to cultivate throughout her career. It was a nascent field, rapidly expanding with fundamental discoveries, but so many questions were still unanswered. However, at the time when she joined Wistar as an assistant professor, the Institute was mainly invested in cancer biology. Oncogenes were protagonists on the cancer research scene and Wistar scientists were pursuing seminal studies on chromosomal alterations, demonstrating their causative role in leukemia. Nishikura was drawn into this line of investigation until the end of the 80s, when a paper by a former MRC colleague came out and described a mysterious biological activity that appeared to unwind double stranded RNA, which immediately caught Nishikura’s attention. “I couldn’t resist looking into it,” she said. “For some time it was my pet project; no study section would believe in it and it was very risky too.”

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That didn’t discourage her, and she kept pursuing the investigation with the resources she could spare from her other projects on oncogenes, which had much more success in securing funds for her lab. “When you find something unusual you have to follow it,” said Nishikura. “Pursuing something unique will make you stand out from the crowd.” This has been her favorite piece of advice for the young scientists training in her lab. “It’s sad and unfortunate that the current climate of high competition for funding pushes young independent investigators away from basic science. They hesitate to embark on risky projects, but these are often the source of breakthroughs.” Nishikura considers herself fortunate to have had major opportunities that gave her the resources and the support to both follow her scientific interest and, at the same time, establish herself as a successful scientist, even though as a young investigator she wasn’t particularly focused on cultivating her academic career. “I was only after my scientific questions and was content to just do my work and search for the answers,” she said. “In retrospect, I was probably naïve, even a little foolish. I didn’t worry much about problems and setbacks. This simplified my decision-making process and helped me stick to it.” Thanks to her determination, Nishikura was able to secure her first grant on RNA editing when she found the gene responsible for the process. The rest is history.

“In the early 90s, RNA editing was a very new concept, with only two or three labs chasing it,” said Nishikura. “Today, it’s a large field with dozens of labs. It’s very satisfying to look back and see that I contributed to opening that path.” The institutes where she trained put her on the right track and equipped her with a successful approach to science, then Wistar was the ideal landing ground to grow and establish herself. “Being at Wistar is a great asset, because of our collaborative environment and vocation of always being at the forefront of new trends and technologies,” said Nishikura. “It has helped substantially when I came across new themes and needed support to acquire different expertise or catch up with new develoments.” Nishikura’s passion and curiosity are unchanged and she still finds great inspiration in science. In 2017, she successfully renewed a large federal grant that had continuously supported her work on RNA editing for 26 years, with a proposal to investigate a novel function she had recently discovered. Outside the Lab

Meanwhile, when not in her lab, Nishikura cultivates other “side projects.” She enjoys traveling the world, especially to places that are interesting from a biological point of view. She recently visited the Galapagos Islands and Antarctica and went on a safari in Africa. The exploration The Gurdon group at the MRC Laboratory of Molecular Biology, Cambridge, component of such trips resonates with her circa 1980. Dr. Nishikura is fourth from the right in the top row. scientific mind. “I love going to music concerts too,” she said. “Whenever I go to Europe for conferences, I try to catch the opera or a classic music concert.” That’s not to say that she doesn’t enjoy some good classic rock. “I’ve recently seen Eric Clapton, the Rolling Stones and Paul McCartney.” At home, Nishikura is an experienced cook, specializing in many types of cuisine. She enjoys cooking for friends and neighbors. “I like cooking because I’m a foodie and because it takes method and creativity, just like science.” These days, she’s been making a tasty and healthy beet salad. She will gladly share the recipe. ■

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SYMPOSIUM RECAP

Honoring Dr. Adel Mahmoud’s Legacy to Improve Global Health

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he Wistar Institute, a birthplace of lifesaving vaccines and vaccine technologies, honored Adel Mahmoud, M.D., Ph.D., an influential leader in vaccine research, development and commercialization, and one of the most respected voices in global health policy. Wistar hosted a full-day symposium held in Mahmoud’s memory that was an opportunity for his friends, colleagues and key leaders in international vaccine research and development to gather and reflect on Mahmoud’s scientific accomplishments, contributions and milestones in the fields of immunology and public health. “Adel was a champion for public health. He always put science first and firmly believed in the power of collaboration and synergy between academia and industry,” said David B. Weiner, Ph.D., executive vice president, director of the Vaccine & Immunotherapy Center, and the W.W. Smith Charitable Trust Professor in Cancer Research at The Wistar Institute, and one of the organizers of the symposium. “These are the principles that inspired his service and dedication to patients.” Elias A. Zerhouni, M.D., retired head of Global Research and Development at Sanofi and former director of the National Institutes of Health, also spoke to Mahmoud’s idea of collaboration between different players towards the universal goal of improving human health through vaccines. “It takes a village to create a vaccine,” said Zerhouni. After a brilliant academic career at Case Western Reserve University, Mahmoud was recruited by Merck in 1998 as president of Merck Vaccines. In this position, he oversaw the development and commercialization of new vaccines against rotavirus, human papillomavirus (HPV), shingles, and the quadrivalent formulation of measles-mumps-rubella-varicella (MMRV). Ken Frazier, CEO of Merck, remembered Mahmoud’s unshakable determination as one of the many characteristics for which he was well-known and well-loved. He applied that determination to make these vaccines available to people and acted as a strong advocate for them to reach the market.

L-R: Drs. Penny Heaton and Stanley Plotkin, Susan Plotkin and Anne Faulkner Schoemaker

“Even after Adel left Merck, he inspired us further, as he launched the initial advocacy for a global vaccine fund for vaccines like the investigational Ebola vaccine,” said Frazier. “It was the power of his inspiring vision and the energy he unleashed in others that has started us down a path that was previously unimaginable.” Distinguished guest speakers at the “Improving Global Health” symposium retraced the scientific challenges and progress behind each of these vaccines and discussed their public health impact and Mahmoud’s instrumental involvement in their advancement. Kathrin U. Jansen, Ph.D., senior vice president and head of Vaccine Research and Development at Pfizer, Inc., told the story of the HPV vaccine: from the discovery of the association between infection and cervical cancer, to the technological advancements that allowed for the development of the vaccine despite technical challenges, to vaccine licensing in 2006 and the significant impact of vaccine implementation on cancer incidence. Mahmoud fought skepticism that the vaccine would not work and stigma for creating a vaccine for a sexually

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“The easy job is to make the vaccine. The more difficult job is to make that vaccine become a policy.” —ADEL MAHMOUD, M.D., Ph.D. 1941-2018

Dr. David B. Weiner welcomes guests at the Improving Global Health Symposium.

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transmitted infection. Without his determination, the HPV vaccine would have probably not made it past the lab. The vaccine is highly effective at preventing cervical cancer, head and neck cancer and other HPV-driven diseases. Penny Heaton, M.D., CEO at the Bill & Melinda Gates Medical Research Institute, spoke to the clinical development of a vaccine against rotavirus, the cause of contagious gastroenteritis that was responsible for 500,000 children deaths each year around the world. Development of this vaccine, said Heaton, is a testament to the magic that can happen when academia and pharma work together towards a common goal, as in Mahmoud’s vision. A rotavirus vaccine developed by scientists at Wistar and the Children’s Hospital of Philadelphia (CHOP) showed 100% efficacy in the early proof of concept studies. Clinical development started in collaboration with Merck, but when another rotavirus vaccine was taken off the market because of reports of serious adverse reactions, the program was halted. Mahmoud knew the devastating effects of rotavirus in developing nations and understood the need and impact of a preventative intervention, so he pushed for a larger clinical trial that would detect any significant adverse event. As a result of his efforts, Merck set up one of the largest trials in history, with 60,000 participants at different sites around the world. The trial showed the vaccine was safe, which in 2006 secured its approval and recommendation by the Center for Disease Control. In the first four years of use in the U.S., the rotavirus vaccine and other vaccines that followed prevented 242,000 emergency room visits for children under five years of age. Rotavirus-related deaths have been reduced by 50% globally. After retiring from Merck in 2006, Mahmoud returned to academia as a professor at Princeton University where he was a key player in the development of the Global Health Program, an interdisciplinary program to prepare the next generation of global health leaders. All symposium speakers remembered Mahmoud as an exceptional mentor and advisor — a kind, energetic and upbeat personality whose clinical and research experience allowed him to understand science well beyond his field of expertise. As Frazier said in his remarks, Mahmoud applied the same passion for developing vaccines to developing the next generation of leaders in the field of global health.

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L-R: Drs. John Mascola, Emilio Emini, Julie L. Gerberding, Jerome Kim, and Paul Offit

“He was always ready to listen. I went to him for advice when faced with challenging issues and he never said no,” said Antony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Disease, in a video tribute presented at the symposium. “He left us with his legacy of enduring achievements that benefited entire fields of medicine.” Mahmoud was a sought-after scientific advisor for many public health organizations, including the World Health Organization, the National Institutes of Health, and the Centers for Disease Control. He served as president of the International Society of Infectious Diseases and on the board of directors of GAVI, The Vaccine Alliance and the International AIDS Vaccine Initiative. He was one of the proponents of a global vaccine development fund with Stanley A. Plotkin, M.D., another giant in vaccine development who worked at Wistar and discovered the rubella and rotavirus vaccines. Their effort led to the creation of the Coalition for Epidemic Preparedness Innovations (CEPI), supported by governments and foundations and launched at the World Economic Forum in Davos, Switzerland in 2017. During Wistar’s symposium, Plotkin talked about CEPI’s mission to support and accelerate the development of safe and effective vaccines against emerging infectious diseases to contain outbreaks before they become global health emergencies. CEPI is the international community’s answer to viral diseases that are not profitable for private

manufacturers to pursue and are tackled by academic labs that lack the resources to take new vaccines and technologies to clinical development. A panel conversation discussed future challenges in vaccine development on the path designated by Mahmoud, including modernizing infrastructures, updating regulations to encourage innovation and improving the public perception of the business of making vaccines. “I’m happy to have the opportunity to contribute to the globalization of a business that used to be restricted to rich countries,” said panelist Julie Gerberding, M.D., M.P.H., executive vice president and chief patient officer, Strategic Communications, Global Public Policy and Population Health at Merck, speaking to the role vaccine development and commercialization companies have played in globalizing the vaccine market and the responsibility that brings the for-profit sector to step up and make investments that will benefit public health. In closing the symposium, Sally Hodder, M.D., associate vice president for Clinical & Translational Science and director of the Clinical & Translational Science Institute at West Virginia University, and Mahmoud’s wife, remarked that the science reflected in the symposium is essential, but not sufficient to benefit all people — across the globe — without the support of the right policies. This perfectly summarizes Mahmoud’s commitment and legacy to vaccine development and global health. ■

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Events Highlights Wistar Party T H U R S DAY, M AY 1 6

In the beautiful setting of the College of Physicians of Philadelphia, Wistar President’s Society donors attended this year’s Wistar Party — an opportunity for the Institute to express gratitude to our most committed supporters. Guest speaker Steffanie Strathdee, Ph.D., associate dean of Global Health Sciences, and Harold Simon Professor at the University of California San Diego, told a fascinating story of how she resurrected an old therapy to save her husband’s life from a deadly, antibiotic resistant superbug. ■

Clockwise from top left: James Wistar and friends; Helen Pudlin, Ron Caplan, The Hon. Harris Hollin and Ellen Caplan; Dr. Steffanie Strathdee, Will Offit and Dr. Paul Offit; guests mingling in the veranda.

Women & Science Program W E D N E S DAY, A P R I L 24

This year’s Helen Dean King Award was presented to Mary-Claire King, Ph.D., one of the most esteemed and productive scientists of our time, in recognition of her seminal contributions to science and human health. King, American Cancer Society Professor at the University of Washington in Seattle, showed that breast cancer is inherited in some families, as the result of mutations in the gene that she named BRCA1. King discussed her storied career, and challenges faced, with an attentive audience at Wistar. ■ Clockwise from top left: Ellen Caplan and Susanna Lachs; Daisy Van Den Hooff-Mertens, Nora McDonald and Dr. Susan McDonald; Dr. Mary-Claire King; Beverly Emanuel, Robin Lovett and Roberta Halpern.

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Noreen O’Neill Melanoma Research Symposium “Heterogeneity, Plasticity and Reprogramming in Melanoma” T U E S DAY, J U N E 1 8

Some of the world’s leading experts in basic and clinical melanoma research gathered at Wistar for this 3rd annual symposium to share the latest discoveries and approaches to care that researchers are developing. Melanoma is a highly heterogeneous disease and is capable of adapting quickly to changing environmental conditions, through the selection of slow-cycling populations with increased intrinsic drug resistance. The close network of more than 200 guests at this symposium provided for an exchange of potential and promising opportunities. ■ Top: Group photo of the Symposium speakers: (L-R, back row) Drs. Meenhard Herlyn, C. Daniela Robles-Espinoza, Alexander Roesch, Ashani Weeraratna, Jean-Christophe Marine, Martin McMahon, Nir Hacohen. (L-R, front row) Drs. Julia Newton-Bishop, Jennifer McQuade, Jessie Villanueva, Julide Celebi, Ze’ev Ronai. Bottom left: Dr. Jessie Villanueva wrapping up the Symposium.

24th Annual Jonathan Lax Memorial Lecture “Discovery and Development of HIV Broadly Neutralizing Antibodies” M O N DAY, J U N E 24

Top right: Juliet Yates, Jane Shull, Dr. Meg Shope Koppel, Bishop Ernest McNear; Bottom right: Drs. Luis Montaner and Michel C. Nussenzweig

Summer 2019

Wistar welcomed guests to this free event that highlights the scientific journey of progress and hope in HIV/AIDS research, treatment and prevention, held each year in honor of leading AIDS activist and businessman Jonathan Lax. This year’s event featured esteemed guest speaker Michel C. Nussenzweig, M.D., Ph.D., Zanvil A. Cohn and Ralph M. Steinm Professor at The Rockefeller University and Howard Hughes Medical Institute investigator.■

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Please join us as we honor the legacy of Fran Tobin with the 2019 Wistar Award.

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THE WISTAR INSTITUTE is an international leader in biomedical research with special expertise in cancer, immunology, infectious disease research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the country, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. The Wistar Institute is an equal opportunity/armative action employer. It is the policy of The Wistar Institute to provide equal employment opportunities to all individuals regardless of race, color, creed, religion, national origin, ancestry, sex, age, veteran status, disability, sexual orientation, gender identity, or on the basis of genetic information, or any other characteristic protected by federal, state, or local law, with respect to all terms and conditions of employment.

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The Wistar Institute is a National Cancer Institute-designated Cancer Center.

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The Wistar Institute Focus - Summer 2019  

The Wistar Institute Focus - Summer 2019