A mechanical method of manufacturing important body chemicals, allowing scientists to study their roles in the growth of cancer, has been devised by researchers in California and Australia.
The new method has already been used to create the largest biologically active protein molecules ever artificially manufactured, an important protein called Interleukin-3. It is a key to the growth of blood cells, as well as a factor in causing one kind of leukemia.
The method and its use to produce IL3 will be reported in Jan. 10 editions of Science magazine by Ian Clark-Lewis, Stephen Kent, Leroy Hood and Ruedi Aebersold of the California Institute of Technology, and Herman Ziltener and John W. Schrader of the Hall Institute of Medical Research in Melbourne.
The method is a more precise version of systems that can join a series of chemicals in the proper order to produce the long, chain-like molecules called proteins.
Previous methods could produce molecules of only 50 amino acids, or "links." Few biologically important molecules are that short.
The new method can produce molecules between 50 and 200 amino acids long, a category that includes numerous important molecules, or parts of molecules, in the body. Interleukins are in that size range. Key parts of antibodies, the molecules that defend the body against infection, also may be made quickly and in quantity by the new method.
The 140-amino-acid molecule produced by the researchers took about 10 days and 15 million steps -- mainly the opening and closing of valves to mix chemicals in sequence -- to make gram-sized quantites, millions of times more than manufactured by the body.
The resulting substance was the IL3 from mice. No one has yet isolated the similar substance from humans, although the two chemicals are expected to be much alike.
In humans and other animals, blood cells are first formed as "stem cells" -- precursors that grow and later produce blood cells with assorted shapes and functions, from the symmetrical red cells to the amoeba-like devouring cells called macrophages.
IL3 is believed to be the factor that triggers the growth and division of the early stem cells. Researchers study its action to see how normal growth becomes the deadly, uncontrolled growth of cancer.
The new method allows researchers to intentionally make altered or defective molecules to see which parts of the molecules are the key, active sites and which can be altered without affecting the molecules' normal actions.
The groups' production of IL3 marks the first time substantial quantities will be available for research.