[Source: House Science and Technology Committee ]
Cheryl A. Nickerson, Ph.D.
Associate Professor of Life Sciences, School of Life Sciences
Center for Infectious Diseases and Vaccinology
The Biodesign Institute
Arizona State University
Mr. Chairman, members of the Committee, thank you for inviting me to appear before you today to testify. My name is Cheryl Nickerson, and I am an Associate Professor in the Center for Infectious Diseases and Vaccinology at the Biodesign Institute at Arizona State University. My research focuses on understanding the molecular mechanisms and processes of infectious disease, with an important emphasis on investigating the unique effect of spaceflight on microbial pathogen responses. NASA’s support of my research has resulted in multiple spaceflight experiments, which have provided novel insight into how microbial pathogens cause infection both during flight and on Earth, and hold promise for new drug and vaccine development to combat infectious disease.
Through awards such as the Presidential Early Career Award for Scientists and Engineers, and independent research funding from grants totaling over three million dollars, NASA has consistently recognized my laboratory’s contributions to the United States Space Program into infectious disease risks for the crew during spaceflight and the general public here on Earth. I also serve as a scientific consultant for NASA at the Johnson Space Center in support of their efforts to determine and mitigate microbial risks to the crew during flight, and was honored to be selected as a NASA Astronaut candidate finalist for the Astronaut class of 2004. That being said, the views expressed in today’s testimony are my own, but I believe they reflect community concerns.
In your invitation letter asking me to testify before you today you asked a series of questions regarding the utilization prospects of ISS research that I would like to address now in sequence.
1. What has been the nature of your space-based research, and what have been your findings to date?
I would like to begin by applauding NASA’s foresight in funding our spaceflight research in the field of infectious disease. We were initially funded by NASA’s Office of Biological and Physical Research and are currently funded by both the Advanced Capabilities Division and the Human Research Program in the Explorations Systems Mission Directorate. The connection between spaceflight and its influence on infectious disease was not immediately clear 10 years ago when NASA initially funded our research. As a result, NASA’s support of my research through multiple spaceflight experiments has allowed us to provide novel insight into the molecular mechanisms that microbial pathogens use to cause infectious disease both during flight and on Earth, and has exciting implications for translation into human health benefits, including the development of new drugs and vaccines for treatment and prevention.
While the eradication or control of many microbial diseases has dramatically improved the health outlook of our society, infectious diseases are still a leading cause of human death and illness worldwide. Infectious disease causes 35 percent of deaths worldwide, and is the world’s biggest killer of children and young adults. Within the United States, infectious disease has a tremendous social, economic, and security impact. Total cost for infectious disease in the U.S. exceeds $120 billion annually due to direct medical and lost productivity costs. Moreover, the future is threatened by new and re-emerging infectious diseases, an alarming increase in antibiotic resistance, and the use of microbial agents as a bioterrorist threat. Thus, research platforms that offer new insight into how pathogens cause infection and disease are desperately needed and will lead to novel strategies for treatment and prevention.
To enhance our understanding of how pathogens cause disease in the infected host, my laboratory uses innovative approaches to investigate the molecular mechanisms of infectious disease. It was this search for novel approaches that drove our initial investigations with NASA technology. As flight experiments are a rare opportunity, our early experimental efforts concentrated on the use of a unique bioreactor, called the Rotating Wall Vessel (RWV), designed at the NASA Johnson Space Center in Houston as a ground-based spaceflight analogue. The RWV bioreactor allows scientists to culture cells (microbial or mammalian) in the laboratory under conditions that mimic several aspects of spaceflight and can be used to induce many of the biological changes that occur during spaceflight. In addition, by using mathematical modeling, we found that this analogue, and true spaceflight, produce an environment that is relevant to conditions encountered by the pathogen during infection in the human host – thus enhancing the relevance of our findings for the development of new strategies to combat infectious disease on Earth.
We chose the model bacterial pathogen Salmonella typhimurium for both our spaceflight analogue and spaceflight studies, as it is the best characterized pathogen and poses a risk to both the crew during flight and the general public on Earth. Salmonella is the most readily and fully understood pathogen and belongs to a large group of bacteria whose natural habitat is the intestinal tract of humans and animals. This group includes most of the bacteria that cause intestinal and diarrheal disease, considered to be one of the greatest health problems globally.
Indeed, Salmonella infection is one of the most common food-borne infections worldwide. In the United States an estimated 1.41 million
cases occur, resulting in 168,000 visits to physicians, 15,000 hospitalizations and 580 deaths annually. Salmonella accounts for approximately 30% of deaths caused by food- borne infections in the United States, and is even more detrimental in the developing world. The total cost associated with Salmonella infections in the US is estimated at three billion dollars annually. Moreover, in 1984, Salmonella was used in a bioterrorism attack by a religious cult in Oregon to cause a community-wide outbreak of foodborne illness in an attempt to influence the outcome of a local election. The organism is also an excellent choice for NASA as it is considered a potential threat to crew health as a food contaminant. There are currently no human vaccines to prevent Salmonella food borne illness.
Using the RWV ground-based technology, we conducted preliminary studies showing that Salmonella responded to this environment by globally altering its gene expression, stress resistance, and disease causing (virulence) profiles, thereby improving our chance of success and need for a spaceflight experiment. Subsequent analysis of the genes that were expressed after growth in this analogue suggested that the environment induced unique molecular mechanisms in the microbe to cause disease. Our information from these early experiments provided NASA with new insight toward understanding the risk of infection during flight. In addition, the unique molecular mechanisms that were identified held the potential to be used to develop new therapeutics and vaccines for the general public on Earth.
NASA and the scientific community continued their support of our ground-based findings by awarding us a grant to investigate the effect of true spaceflight on Salmonella virulence and gene expression responses. This was an exciting opportunity for us, as while the RWV bioreactor can simulate some aspects of the spaceflight environment, it cannot duplicate all of the physical parameters that organisms encounter during spaceflight or their biological responses. In September 2006, our first spaceflight experiment flew aboard STS-115, and we investigated the comprehensive changes in Salmonella when exposed to the truly unique environment of microgravity. The results from this experiment were remarkable and showed that during spaceflight, Salmonella altered its virulence and gene expression responses in unique ways that are not observed using traditional experimental approaches.
These findings immediately advanced our knowledge of microbial responses to spaceflight and disease causing mechanisms used by this important human pathogen. Our first technical report from this spaceflight experiment was recently published in the Proceedings of the National Academy of Sciences, and our results demonstrated changes in Salmonella disease causing potential (virulence) during flight as compared to identical samples that were grown on the