Mar 29, 2002

Antibiotics from Space




Test tubes of bacteria produce more antibiotics in space than they do on Earth. Researchers aren't sure why ... but they aim to find out.




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March 29, 2002: Bacteria get no respect.

People wash their hands with anti-bacterial soap. The most popular nickname for bacteria is "bugs." And, by the way, don't touch that doorknob!

Yet, bacteria are not always a bad thing. They don't just cause sickness, they help cure it: the antibiotics prescribed for your toddler's earache, for example, were most likely harvested from the microbes themselves.

Right: A microbiologist using a microscope studies bacteria cultured in petri dishes.

Because people need antibiotics, some scientists are working hard -- not to kill but to nurture bacteria. A good place to do that, it seems, is in space. Researchers first noticed in 1968 that microbes cultured onboard NASA's Biosatellite II grew better than they did on Earth. That raised an obvious question: If microbes grow better in space, would they produce more antibiotics there, too?




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The answer is yes -- under certain conditions. Experiments sponsored by Bristol-Myers Squibb in the mid-1990's revealed that microbes grown in test tubes or gas-permeable bags aboard the space shuttle produced more antibiotics than did microbes on the ground. In one case the improvement was as much as 200%. Antibiotic production is an important part of the pharmaceutical industry on Earth, so this result caught the attention of scientists and business people alike.

Is it time to move antibiotic factories to space? Not yet. Sophisticated bio-reactors on Earth still yield more antibiotics than simple test tubes or bags do on orbit. The value of space -- for the moment -- is as a laboratory.

The ongoing research is supported by BioServe Space Technologies, a NASA Commercial Space Center (CSC) at the University of Colorado, industry partner Bristol-Myers Squibb, and NASA's Space Product Development program. Their goal is simple: to find out why microbes yield more antibiotics on orbit, and apply those findings to increase yields on Earth.

Below: A gas-permeable bag full of space-grown bacterial colonies (right) alongside a matched ground control (left). Production of the antibiotic Actinomycin D was 75% greater in the 0-g bag, which flew on Space Shuttle mission STS-95 in 1998. Credit: BioServe Space Technologies.


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It's possible that the increase occurs simply because of the way microgravity alters the motions of fluids surrounding the bacteria, says BioServe associate Director David Klaus, who co-heads the study.

On Earth, gravity causes the fluid -- that is, the medium -- to circulate. Heavier fluids fall and lighter ones rise. Within the medium, cells and the molecules they produce mix and move around. "But in a zero-g environment," points out Klaus, "there is no convection, or buoyancy, or sedimentation." Less of the mixing normally caused by such factors could change the metabolic activities of these one-celled creatures.

For example, when bacteria are introduced into a new environment, they don't start multiplying immediately. First, they have to 'condition' themselves or their surroundings. That is the reason that you can leave food out for a while before it begins to spoil. Researchers speculate that bacteria produce vitamins, enzymes or other "cofactors" either inside or around the cell. Cells will begin to multiply only when enough of those substances have accumulated.

In microgravity, the bacteria seem able to achieve this conditioning and begin growing sooner than they can on the ground -- perhaps because of reduced mixing. If a cell excretes a certain type of molecule, those molecules stay closer, and their concentration increases faster. The same kind of change, Klaus suggests, might account for the increased production of antibiotics.

In fact, no one knows exactly why microbes produce antibiotics at all. One possibility is that antibiotics are produced in response to stress. In space, says Klaus, the stress that triggers the production of antibiotics might simply result from the altered environment around the cell -- like a buildup of nearby wastes.


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Or, the overproduction might reflect some unknown change within the cell itself.


An upcoming experiment on the International Space Station (ISS) will help solve the puzzle. Engineers at BioServe have developed a system known as MOBIAS: the Multiple Orbital Bioreactor with Instrumentation and Automated Sampling. MOBIAS, explains Klaus, provides bacteria with roughly the same environment whether they are in space or on the ground.

Rather than requiring gravity to mix the gases and nutrients, MOBIAS relies on diffusion. Diffusion -- a mixing caused by the random thermal motions of molecules -- occurs both on Earth and in space.

Above: A photo of MOBIAS. Credit: BioServe Space Technologies.

To accomplish its purpose, MOBIAS grows microbes in long, thin gas-permeable bags. The fluid medium is kept in narrow layers -- much like sandwich fillings -- so that only diffusion and occasional small injections of extra fluid provide the cells the gas and nutrients they need.

Of course, the space and ground systems won't be precisely alike. In 1-g, the cells will still end up on the bottom of the container. But, says Klaus, the difference should be minimal, because in this case, the bottom isn't very far from the top!

And, he adds, Earth-gravity will still pull on the cells themselves. That's good because that is one effect that they are trying to isolate.


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MOBIAS is slated for launch on April 4, 2002, inside BioServe's Commercial Generic Bioprocessing Apparatus (or CGBA for short). Space Shuttle Atlantis will carry the CGBA aloft and leave it behind on the ISS where it will remain for at least 68 days -- longer than any single shuttle flight. "One of the advantages of the ISS," notes Klaus, "is that on station we can run these experiments for many weeks or months." (In earlier work, shuttle-based samples didn't always have time to reach peak production before the mission ended.)

Left: Antibiotic production is big business on Earth. The global annual market is valued at more than 20 billion dollars.

Will MOBIAS in space outperform MOBIAS on the ground?

"I suspect that we will see an increase [on orbit], but we've got to run the test to find out," says Klaus. If the bacteria do overproduce, and researchers can figure out why, those factors could be mimicked in terrestrial facilities. Even a tiny increase in production efficiency, explains Klaus, would be very significant commercially: one estimate holds that each one percent increase
in efficiency would save around six million dollars annually in antibiotic production costs.

Such prospects have researchers paying close attention to these tiny microbes. No respect? No way.


More information

Space Product Development -- The goal of NASA's Space Product Development (SPD) program, managed from the Marshall Space Flight Center, is to help American businesses explore the potential--and reap the rewards--of doing business in space. SPD helps bring the benefits of space down to Earth where it enriches the everyday lives of the American public.

Bristol-Myers Squibb Pharmaceutical Research Institute -- this Industry Partner works with BioServe and NASA to study antibiotic production in space.


Right: A test tube full of space-grown bacterial colonies (right) alongside a matched ground control (left). Production of the antibiotic Monorden was 200% greater in the 0-g test tube, which flew on Space Shuttle mission STS-77 in 1996. [more] Credit: BioS Technologies.

BioServe Space Technologies -- a non-profit, NASA-sponsored Commercial Space Center (CSC) located jointly at the University of Colorado in Boulder, Colorado, and Kansas State University in Manhattan, Kansas (BioServe-KSU), established in October 1987. NASA's Space Product Development (SPD) program, located at the Marshall Space Flight Center, encourages the commercialization of space by industry through 17 such CSCs.

Antibiotic links: What the Heck is an Antibiotic? (Bugs in the News);

US BioSatellite Program -- In the late 1960's researchers discovered that bacteria grow better in space.


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