Science: Man-Made Penicillin

The blue-green mold, Penicillium notatum, which excretes penicillin, has a laboratory rival. Last week a biochemical team led by Dr. Vincent du Vigneaud of the New York Hospital-Cornell Medical

Center proudly showed some brown crystals which they had synthesized and proved to be one of many varieties of penicillin: “penicillin-G.”

Almost as soon as penicillin was isolated, chemists tried to make it artificially. The job was tough, for the penicillin molecule is unstable and exceedingly complex. Frantic wartime efforts by the British and OSRD (Office of Scientific Research and Development) did much of the pioneer work; the Cornell group finished the job.

The general method, as in most syntheses, was to break down natural penicillin-G into simpler compounds which could be made artificially, then try to make these combine into penicillin. Dr. du Vigneaud and his associates started (as others had before them) with two decomposition products—dextro-penicilla-mine hydrochloride and 2-benzyl-4-meth-oxymethylene-5(4)-oxazolone. Over & over again they made them combine under different conditions.

In some cases the product was a rather feeble germ-killer. But this did not prove that it contained real penicillin, for many structurally unrelated chemicals kill germs. So the biochemists put their best synthetic germ-killer through a long series of grueling tests to compare it with real penicillin-G.

Radioactive Tracer. The most spectacular test used radioactivity. A little of the unknown synthetic which the chemists hoped was penicillin was made up with radioactive sulphur built into its molecule. Mixed with natural penicillin, it was put through recrystallizations and chemical transformations.

The molecules containing radioactive sulphur could be traced with Geiger counters. If they had wandered off by themselves, they would have proved that they are different chemically from natural penicillin. But they followed it faithfully through all the processes, proving that the composition was identical.

Next step: to separate synthetic penicillin in pure crystalline form. The most successful separation method used two liquids which do not mix. Since one dissolved penicillin more readily than the other, penicillin concentrated in it, leaving unwanted substances behind. The process had to be repeated again & again, but finally the biochemists got their pinch of brown crystals: the first pure man-made penicillin.

Cheaper & Better? Dr. du Vigneaud does not claim that this process can compete economically at present with the vats of slimy blue-green mold which produce natural penicillin. But he points out that synthetic methods usually become more efficient with practice and as they are better understood. Eventually, synthetic penicillin may be cheap enough to treat the poorest patient.