Bristol Myers Squibb Research Shows Promising Results

Bristol Myers Squibb Pharmaceutical Research Institute, working with BioServe Space Technologies, sponsored experiments on STS 95 in October 1998 to study the on-orbit manufacture of actinomycin D. The drug is used in chemotherapy. Results from the STS 95 research indicate production could be increased 75% by on-orbit processing, over comparable terrestrial processes. Earlier pilot studies showed up to 200% increases in antibiotic production by space-grown cultures over control cultures. Increasing production of any antibiotic, even slightly, is considered significant by the pharmaceutical industry.

David Klaus, an assistant professor of Aerospace Engineering Sciences at the University of Colorado-Boulder and associate director of research for BioServe Space Technologies, commented, “With just some very crude calculations, we've estimated that even something like a 1 percent increase in production could feasibly result in about US$6 million in savings.” Klaus believes, space represents a "last frontier" in terms of opportunities to increase production rates for antibiotics. 

Antibiotics represents the most valuable segment of the pharmaceutical industry, with the global annual market exceeding $US20 billion. Antibiotics are traditionally manufactured using fermentation processes to stimulate the over-production of primary or secondary metabolites by microbes. Early space flight research, dating back to the 1960’s, has indicated that bacterial growth is enhanced when cultured in microgravity.

There are three aspects to producing an antibiotic on Earth. One, the cell can be optimized, two, the growth medium can be optimized or, three, the process efficiency can be optimized. Klaus says, “The first two are thought to be pretty well played out, so anything to increase the efficiency of producing these things back on earth has the potential to be a tremendous cost savings.” BioServe Space Technologies initiated a research plan in 1990 to systematically quantify the effects of space flight on bacterial growth while simultaneously evolving the design of a space bioprocessing payload over numerous shuttle missions. Pilot studies were carried out on shuttle missions STS 77 in May 1996 and STS 80 in November 1996, in addition to the STS 95 mission.

The two initial flight experiments were conducted in test-tube-like devices, but this generic hardware has since been evolved into a more optimal “zero-gravity fermentor” design. BioServe Space Technologies, Boulder, Colorado, designed and built the automated gas-exchange fermentation system which was used in the STS 95 experiments.

A 10-14-day space shuttle mission does not allow time to decipher real changes or trends in fermentation. A 24-month space station mission is scheduled to begin in April 2001. Those experiments will involve multiple sets of inoculation, growing and regrowing many generations of bacteria in microgravity and taking samples along the way to analyze their production rates and changes at various stages.

Space flight pharmaceutical research has introduced the possibility of obtaining novel insight into fermentation processes by removing the normally present influence of gravity from the cell and their environment. Companies currently conducting research into on-orbit antibiotic production are not presently planning to manufacture antibiotics in space, but are just trying to understand the mechanisms that improve antibiotic production, and then apply the knowledge they learn to improve their terrestrial processes. The current focus is to learn more about the effects on gravity and how it affects the physical nature of things.

BioServe Space Technologies is a NASA Commercial Space Center (CSC) located jointly at the University of Colorado in Boulder, Colorado and at Kansas State University in Manhattan, Kansas. BioServe’s mission is to develop new or improved products through space life science research in partnership with industry, academia and government.

Bristol Meyers Squibb, Princeton, NJ, revenues exceeded US$20 billion in 1999, with about 37 percent of those sales outside the U.S. Companywide research and development spending in 1999 exceeded US$1.8 billion. Bristol Meyers Squibb employs more than 54,000 employees in over 60 countries.

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