Research Roundup: inclusion of women in clinical trials, the future of vaccines, and diagnostics for counterfeit medicines and parasitic worms

How can we get Big Pharma to invest in low-cost antibiotic research and development (R&D)? The Review of Antimicrobial Resistance—a research group led by economist Jim O’Neill and established by United Kingdom Prime Minister David Cameron—proposed innovative answers to this question in its recently released third report, focused on the R&D pipeline for antibiotics. The report calls for the creation of a fund worth US$16 to 37 per decade to provide cash incentives of $2 to 3 billion for pharmaceutical companies that develop new antibiotics and agree to sell them on a not-for-profit basis. Additionally, the report calls for the creation of a Global Antimicrobial Resistance Innovation Fund, worth $2 billion, to support basic research into antibiotics and diagnostics that would enable the strategic use of antibiotics by primary care physicians. O’Neill reiterated that the cost of inaction around antimicrobial resistance could be as high as $100 trillion and 10 million lives by 2050, as detailed in the first report. A group of experts, including Executive Director Bernard Pécoul of the Drugs for Neglected Disease initiative—a member of the GHTC—are calling on governments and other donors to establish a pooled fund to address R&D gaps for antimicrobial resistance, emerging infectious diseases, and neglected diseases. The experts address the aforementioned proposal to incentivize R&D for antibiotics, warning against a fragmented approach, and calling for coordination in not only financing, but throughout the R&D process. Liberia is now considered free from Ebola, after 42 days—twice the maximum incubation period—without a new case, and Guinea and Sierra Leone reported only seven and two cases last week, respectively. As the West African epidemic comes to a close, clinical trials for experimental Ebola vaccines and drugs are underway. The World Health Organization (WHO) hopes that it will be able to test the efficacy of the two drugs, Zmapp and sIRNA, but realizes that it may be challenging to determine the efficacy of the two vaccine candidates, developed by GlaxoSmithKline and a partnership between Merck and NewLink Genetics. Marie-Paule Kieny, assistant director-general for health systems and innovation at the WHO, noted that there are alternative forms of efficacy testing, such as the “Animal Rule,” under which the US Food and Drug Administration will approve a vaccine if it has proven safe for humans and effective in animals with similar immune systems as humans. This rule can be applied for rare diseases or in cases where testing on humans would be unethical. The WHO also hosted an experts meeting on Ebola R&D last week, with the goal of creating a framework for expediting R&D in future outbreaks. While Kieny highlighted recent progress, with drug and vaccine candidates for Ebola moving through the pipeline in months rather than years, an existing framework would allow the WHO to respond rapidly. TB Alliance, a member of GHTC, has initiated clinical trials of “Nix-TB,” the first, all-oral drug regimen for extensively drug-resistant tuberculosis (XDR-TB). TB Alliance is sponsoring the trial in partnership with Janssen Pharmaceutica—who provided a royalty-free license for one of the drugs in the regimen—and three hospitals in South Africa where Nix-TB is being tested. The regimen is comprised of three drugs, including one that is currently undergoing clinical trials independent of Nix-TB and a general antibiotic that has been used off-label to treat TB. There is currently no approved treatment for XDR-TB, and only 16 percent of patients receiving treatment are cured after two years. According to TB Alliance President and CEO Dr. Mel Spigelman, “The launch of Nix-TB is a critical step to achieve the vision of a truly short-course, simple, affordable, and well tolerated universal treatment regimen.”

Breakthrough ideas are like children—they start small, they need constant nurturing, they don’t always develop according to schedule, but they change lives forever. In honor of Mother’s Day, GHTC is highlighting the stories of five mothers who have given birth to scientific discoveries or bold ideas that have transformed global health. 1. Ruth Bishop (b. 1933), Discoverer of Rotavirus Ruth Bishop at work in her lab. Photo: Stepping Stone Pictures As a young bacteriologist working in the 1970s, Ruth Bishop was on a quest to find the root cause of diarrheal disease—the most common illness among children worldwide. After much research, Bishop concluded that the disease was likely not caused by a bacterial agent, but instead by a virus. To continue her search, Bishop teamed up with two colleagues at the University of Melbourne – virologist Ian Holmes and electron microscopist Brian Ruck. In 1973, using an electron microscope, the team uncovered a previously unidentified virus in the biopsy sample from an intestinal lining. Bishop and her team went on to confirm presence of the virus in other samples. Their published results elicited a global response and confirmation of the virus’s presence in samples around the globe. The virus identified by Bishop and her team would come to be named rotavirus for its wheel-like shape. Rotavirus is the leading cause of severe diarrhea in children worldwide and affects nearly every child in their first three years of life. Bishop and her team went on to develop a diagnostic test for the virus, and their continued research helped pave the way for the development of a rotavirus vaccine which was introduced more than three decades after their initial discovery. Today there are two rotavirus vaccines commercially available with additional candidates in the research pipeline. Gavi, the Vaccine Alliance estimates that by 2030, 2.4 million lives could be saved through rotavirus immunization. Bishop, who is the mother of one son and is now officially retired, has watched these vaccine developments with excitement. “Rotavirus will always be around,” she said, “but we can stop it from being a killer.” For more information on Ruth Bishop, check out this Science in Public article. 2. Rosalyn Sussman Yalow (1921-2011), Unlocked breakthrough diagnostic technique Rosalyn Yalow at Bronx Veterans Administration Hospital in October 1977. Photo: US Information Agency Rosalyn Sussman Yalow knew by the age of eight that she wanted to be a scientist. Despite living in a time when few scientific opportunities were available to women, Yalow remained undeterred in her pursuit. After completing her master’s degree and PhD in physics while working as an electrical engineer and college instructor, Yalow decided she wanted to be a full-time researcher. Unable to find a research position, Yalow decided to volunteer at a Columbia University radiological research laboratory. There she was introduced to the emerging field of radiotherapy. A few years later in 1950 while working at the Bronx Veterans Affairs Hospital, Yalow would meet and begin working with her lifelong research collaborator Solomon Berson. Together the two would develop radio-immunoassay, a technique that used radioactive isotopes as markers to trace and measure concentrations of hormones, viruses, enzymes, and other substances in the body. Their discovery of this technique revolutionized biological and medical research and made possible the development of diagnostic tests for infertility, hypothyroidism, and dwarfism; and screening tests for infectious diseases such as hepatitis and HIV and AIDS in blood donations. In 1977 Yalow became the second woman to earn a Nobel Prize in medicine. A mother of two children, Yalow advocated for the advancement of women in sciences. In her Nobel Prize banquet speech, she said of women, “We must believe in ourselves or no one else will believe in us; we must match our aspirations with the competence, courage, and determination to succeed, and we must feel a personal responsibility to ease the path for those who come afterward.” For more information on Rosalyn Sussman Yalow, check out her bio on the American Chemical Society website or her obituary that appeared in The New York Times. 3. Flossie Wong-Staal (b. 1947), Leading HIV and AIDS researcher Flossie Wong-Staal at the National Cancer Institute. Photo: National Cancer Institute/Bill Branson At the age of 18, Flossie Wong-Staal left Hong Kong to pursue her passion for biology in the United States. After completing her PhD in molecular biology in 1972, Wong-Staal moved to Bethesda, Maryland to study retroviruses with pioneering AIDS researcher Robert Gallo at the National Cancer Institute. Together they searched for the cause of AIDS, which was by then spreading in the United States. In 1983, Wong-Staal, Gallo and their team discovered HIV, the virus that causes AIDS. Two years later, Wong-Staal became the first scientist to clone and produce a genetic map of the virus, both of which were critical steps toward the development of blood tests for HIV. Wong-Stall continued her research on the HIV virus for over a decade, and today she help leads a biopharmaceutical company she co-founded which is working to develop improved drugs for Hepatitis C. Wong-Staal, who is the mother of two daughters, said of her interest in research, “For me, as for most researchers, the main motivation is simply the satisfaction of making discoveries, finding things out that no one knew before.” 4. Dorothy Hodgkin (1910-1994), Mapped the structure of penicillin Dorothy Hodgkin demonstrates the structure of vitamin B12 with a model. Photo: C&EN Archives Born in the early twentieth century, Dorothy Hodgkin was a trailblazer for women interested in the sciences. As a teenager, Hodgkin received as a birthday gift from her mother a book by Nobel Prize–winning physicist William Henry Bragg that discussed using X-rays to “see” the three-dimensional structure of molecules. This present would change the course of her life. Fascinated by the ideas presented in the book, Hodgkin would make the study of this field her life’s work. After graduating from college, Hodgkin found a position in an x-ray crystallography lab where she went to work studying the complex organic molecules that help a living organism function. The technique she used involved crystallizing the substance she was studying, shooting X-rays at it, and then studying the ways the X-rays refract off the structure in order to determine its shape. In 1946, after four years of studying the antibiotic penicillin using this technique, Hodgkin determined its structure, marking an important advancement which would help manufacturers create semisynthetic penicillin. Over the course of her career, Hodgkin also determined the structure of vitamin B12 and insulin. In 1964, she became the third woman to win the Nobel Prize in chemistry. A mother of three children and grandmother of three grandchildren, Hodgkin said of her career, “I was captured for life by chemistry and crystals.” For more information on Dorothy Hodgkin, check out her bio on the Chemical Heritage Foundation website or Nobel Prize website. 5. Margaret Sanger (1879-1966), Birth control pioneer Birth control pioneer Margaret Sanger. Photo: public domain Margaret Sanger devoted her life to expanding the availability of birth control and contraceptive options for women. Sanger’s devotion to this cause was born out of personal tragedy. At age 19, Sanger watched her mother—who gave birth to 11 children and suffered seven miscarriages—die of tuberculosis. Sanger believed that her mother’s repeated pregnancies had weakened her body’s ability to fight the disease. Wishing to build a different life for herself, Sanger became a nurse. Serving the people of New York’s Lower East Side, Sanger tended to the needs of impoverished women who lacked effective options to prevented unwanted pregnancies and often resorted to back-alley abortions in desperation. This experience deepened Sanger’s resolve that women needed access to safe and effective contraceptives so they could stay healthy, limit their family size as desired, and break the cycle of poverty. As a young mother of three children, Sanger switched her focus from nursing to advocating for the legalization of birth control and making it universally available to women. Although Sanger experienced several legal victories over the next three decades which expanded contraceptive access, she remained frustrated by the lack of birth control options available to women and dreamed of a contraceptive pill that would be as easy to take as a vitamin. To make that dream a reality, she recruited reproductive health researcher Gregory Pincus and raised the needed funding from heiress Katharine McCormick. This collaboration would lead to the development and introduction of the first oral contraceptive in 1960. Today Sanger’s vision of a world where all women have the ability to prevent or space their pregnancies remains only partially realized. Although more than 99 percent of American women have used a contraceptive method in their lifetime, an estimated 222 million women in developing countries want to limit or control the timing of their pregnancies but lack access to modern contraceptives. Said Sanger, “No woman can call herself free until she can choose consciously whether she will or will not be a mother.” For more information about Margaret Sanger, check out her bio at the National Women's History Museum website or PBS website.