Scientist/astronaut to study white blood cell dysfunction in space

A biological experiment on board the International Space Station (ISS) will be used to probe the mystery of why a part of the human immune system fails to function normally in the weightless environment of space.




“Lowered immune function in astronauts has been observed for decades,” says the experiment’s designer, former astronaut Millie Hughes Fulford, PhD, a research scientist at the San Francisco VA Medical Center (SFVAMC). Hughes-Fulford’s experiment will test whether white blood cells called monocytes fail to respond to infection in a normal way under weightless conditions.


Monocytes, which circulate freely in the bloodstream, ordinarily react to infection by maturing into their active form, known as macrophages, which then adhere to infected tissue and engulf bacteria and viruses. Hughes-Fulford believes that in the absence of Earth’s gravity, monocytes do not mature.


The experiment will be conducted by astronauts aboard ISS under the direction of Hughes-Fulford on Earth. It will be carried to ISS aboard a Soyuz spacecraft that is scheduled for launch on October 10 from Baikonur, Kazakhstan. The mission will be operated by the European Space Agency. 


“Fifteen of the 29 Apollo astronauts had bacterial or viral infections, including gastroenteritis and upper respiratory infections, either during spaceflight or within a week after,” says Hughes-Fulford, an adjunct professor of medicine at the University of California, San Francisco (UCSF) who was a payload specialist aboard shuttle flight STS-40 in 1991. “Subsequent studies in shuttle astronauts have shown lowered monocyte levels and reduced macrophage function. These observations, plus experiments that we have conducted under conditions of artificial microgravity on Earth, suggest that monocytes do not mature into macrophages in microgravity.”



Hughes-Fulford believes the reason is a lack of gene expression in the monocytes. “In our microgravity experiments on Earth, certain genes that normally start the molecular signaling cascade that leads to monocyte maturation are not expressed,” she says. “Our experiment aboard ISS will tell us if those same genes don’t turn on in space.”
The experiment, with human monocytes in a culture medium, will be packed aboard the cramped Soyuz inside a specially designed incubator designed to fit precisely under the pilot’s seat. Once on board the space station, the incubator will heat the cells to body temperature—37 degrees Celsius. An astronaut will then add an activator that, in gravity, normally starts the molecular cascade that causes monocytes to mature into macrophages.


Three hours later, says Hughes Fulford, “we check to see if any of the early molecular signals are dampened by lack of gravity. This will give us a major clue to see if there’s a biological signal system that’s broken.”


Twenty-four hours later, the ISS crew will check to see if any of the monocytes have matured into macrophages.


Hughes-Fulford and her research team, who are hand-carrying the experiment to Baikonur from San Francisco, will analyze the results in detail after the experimental apparatus has been brought back to Earth aboard a returning Soyuz. “We are looking at the entire human genome contained in the cells,” she says. “So we will know, out of 30 thousand-plus genes, which ones aren’t turned on.”


In 2006, Hughes-Fulford oversaw a similar experiment aboard ISS which showed that T cells, the white blood cells that are the target of HIV infection, do not activate in a weightless environment because certain T cell genes fail to express. She hopes that if the current experiment goes as planned, she will be able to trace the two failures back to the same genetic source.


“This is all part of the general human immune response,” she observes. “My hope is that we’ll pinpoint one or two molecular pathways common to both failures—perhaps one key molecule that normally starts the whole cascade isn’t being made. And then we can start looking at possible treatments—what turns the system back on.”


Hughes-Fulford maintains that the mystery of immune system failure must be solved if humanity is ever to explore and colonize space. “Given how long it will take just to travel to Mars and back—about a year and half round trip—we have to overcome this problem,” Hughes-Fulford says. “If we don’t, a simple infection could turn into a catastrophic epidemic for an entire exploration team.”
She notes that the current experiment is the last scheduled American biological experiment in space, “but my hope is that our work will inspire a change.” 


Accompanying Hughes-Fulford to Baikonur are Tammy Chang, MD, PhD, a surgical research fellow at SFVAMC, and Chai-Fei Li, BS, a research associate at the Northern California Institute for Research and Education (NCIRE).


The experiment is supported by funds from the National Aeronautics and Space Administration (NASA).


NCIRE - the Veterans Health Research Institute - is the largest research institute associated with a VA medical center. Its mission is to improve the health and well-being of veterans and the general public by supporting a world-class biomedical research program conducted by the UCSF faculty at SFVAMC.


SFVAMC has the largest medical research program in the national VA system, with more than 200 research scientists, all of whom are faculty members at UCSF.


UCSF is a leading university that advances health worldwide by conducting advanced biomedical research, educating graduate students in the life sciences and health professions, and providing complex patient care.