Toward a Safer Penicillin

The many varieties of penicillin have a unique disadvantage: about one in a hundred patients who get them by injection becomes sensitized, so that his next shot may produce a severe reaction marked by rash, fever, swollen glands and pain in the joints. In a few cases, the response is so fast and catastrophic that it is called anaphylactic shock, a violent reaction usually associated with the introduction of foreign protein into the system. A patient thus afflicted may die within minutes.

To Dr. J. George Feinberg, a U.S. immunologist working at Britain's Beecham Research Laboratories, the killing power of penicillins made no sense.

Since penicillin molecules are not proteins, he reasoned, they must somehow get hooked up to a protein. Sure enough, when he had basic penicillin preparations put through careful laboratory separation procedures, two fractions appeared: a pure penicillin that did not cause reactions in sensitized guinea pigs and a minute quantity of a second substance that produced violent reactions. This second substance proved to be a large protein molecule, with part of the penicillin molecule attached. The protein can be removed in the final stages of manufacture, thus making injected penicillin much safer for the non-sensitized patient.

Other purification procedures yielded a second impurity. Not a protein, it appears to be a product of the penicillin molecule itself, which forms spontaneously after penicillin is stored for even a short time. As its formation cannot be completely prevented, penicillin injections for patients known to be sensitive are still too risky.

The findings reported in the Lancet by three research groups go far to ex plain another mystery of penicillin --why it is so much less likely to cause severe reactions when taken by mouth than when injected. It seems that much of the protein impurity is destroyed -- digested, in effect -- in the alimentary tract before it can get into the bloodstream.

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