Even Hell Hath Its Peculiar Laws

The legend undoubtedly has origins that predate the short German chapbook published in 1587 that tells the story of Johann Fausten.  A scholar at Wittenburg, Dr. Fausten’s thirst for knowledge is unquenchable.  When he feels that he has learned all that he possibly can, he turns to magic and, seduced by the power of the black arts, summons Mephistopheles as the representative of Lucifer.  The two negotiate and hammer out an agreement to be signed in blood in which Dr. Fausten will sell his soul in exchange for twenty-four years of power and Mephistopheles as a servant to his every whim.  Dr. Fausten indeed enjoys a time of great power, but in the end it is seen as a pittance when measured against the loss of his soul to eternal damnation.

The lesson of the legend of Faust, which recurs time and again in the course of human events, is that there are bargains we make that have consequences far worse than we imagine when we are seduced by the power that we can temporarily achieve with the bargain.

Physicians, confronted with the increasing resistance to antibiotics, are beginning to flirt with a seductive possibility.  The story of antibiotics is one that is well known.  It was 1928 and Dr. Alexander Fleming was working at St. Mary’s Hospital in London as a bacteriologist.  One day, he returned to a plate culture of staphylococcus to find it contaminated with a blue-green mold.  It was probably a moment of frustration, to find the contamination, but there was something interesting about it.  Bacteria colonies next to the mold (Penicillium) were being dissolved.  Fleming grew the mold in pure culture, leading to the discovery of penicillin, a substance produced by the mold and that had antibiotic properties.  Penicillin itself was not chemically isolated until World War II, earning Howard Florey and Ernst Chain the Nobel Prize in medicine.

The discovery of antibiotics revolutionized the treatment of infectious disease.  Physicians were given a miraculous cure for battling bacterial infections and through the last half of the twentieth century, it became commonplace for those who fell ill to rely on the availability of a simple pill to cure much disease.

But the promise of antibiotics was in some respects short-lived.  The mechanisms of natural selection operated on the genetic structure of bacteria when they were exposed to antibiotics, causing them to mutate into resistant strains.  Already in the 1950’s — little more than ten years after the isolation of penicillin — it was apparent that tuberculosis bacteria had undergone mutations to make it resistant to streptomycin.  Over time, things have worsened.  Widespread use of antibiotics has resulted in so many resistant bacterial strains that many antibiotics are all but useless.  And so enters the possible Faustian bargain.

As more and more antibiotics were being discovered, some were found to have high toxicity.  One example was chloramphenicol, which can produce aplastic anemia in some patients.  There is no known way to predict who may or may not get this side effect and it is generally fatal.  It can also cause inner-ear damage that produces tinnitus and balance problems and may be linked to chronic lymphcytic leukemia.  But even so, many physicians are now looking to chloramphenicol as a viable antibiotic in treating bacterial strains that have become resistant to even the most powerful antibiotics that are currently used and safer.  Many feel they have little choice.  There are few new antibiotics being developed and these old ones have the advantage that they have been so little used that bacteria have not had a chance to develop resistance.

The legal issues related to the use of antibiotics centers around regulatory approval processes.  This week, Lannett Co. in Philadelphia announced that it has formulated capsules of chloramphenicol with ingredients from a Spanish supplier with the intention of seeking approval from the Food and Drug Administration for oral use of chloramphenicol “as a drug of last resort.”

Is this a compromise of the type that Faust made with Mephistopheles, a bargain for greater power now over the treatment of infectious disease that has consequences we do not fully appreciate?  Only time will tell, but what is certain is that after less than a century, physicians are already seeing the need to compromise as the wonderful promise of Alexander Fleming’s discovery appears to be reaching its limits.