Monday, March 05, 2007

Some Historical Problems in the Production of Useful Penicillin

Survivors of an Eschaton event may encounter many of the same problems as the historical discoverers when producing new technologies, such as penicillin. Therefore, it is useful to study creative, low-tech solutions to these problems.

Penicillin is an acid produced by some strains of the mold species now known as Penicillium chrysogenum. There has been some confusion historically surrounding this choice of name, because Fleming, the original discoverer of the antibiotic action of penicillin, used the term "penicillin" to refer to the unpurified "mold juice" produced when P. chrysogenum is grown on, say, beef broth, and Florey and later investigators applied the term "penicillin" to refer to the purified antibiotic chemical. It is important to keep these two uses straight in one's mind - injecting "mold juice" into a person would cause death by anaphylactic shock because of all the impurities in the product, whereas purified penicillin is only dangerous to those who are allergic to the substance. I will follow Lax and generally use the colloquial but very descriptive "mold juice" to refer to the unpurified product, and "penicillin" to refer to pure penicillin. At any rate, penicillin, a product of the mold P. chrysogenum, was discovered as early as 1929, but was not purified into a form useful for treating humans until 1941. Researchers encountered several problems along the way; post-Eschaton scientists may expect to encounter any of the following problems:

  1. Locating the right strain of the right mold. The mold that produces penicillin is not just any mold, but specifically the mold Penicillium chrysogenum. (The mold involved in the original research on penicillin was then known as P. notatum, which was "found in decaying hyssop in Norway" (Herrell, 1945). P. notatum has since been taxonomically merged with the species P. chrysogenum. It is an extremely variable species, and many strains have been identified and even created by mutation under UV light or X-ray. Strains vary WIDELY in their efficiency in producing penicillin.) This mold must be located, identified, cultured, and tested for penicillin production, before biological synthesis can occur. Stay tuned for next post regarding an ingenious plan devised by Florey's British research team during World War II to preserve cultures of the mold in case the Germans took over their lab.
  2. Growing large quantities of "mold juice," and/or improving the penicillin yield of the mold juice. Nearly 100 liters of mold juice were required by Florey and his collaborators to produce one day's dose of penicillin; several modifications over the years made biological production of penicillin much more efficient. (Ibid.)
  3. Extracting the penicillin from the mold juice. Florey collaborator Heatley devised a fairly ingenious way to extract pure penicillin from mold juice. The mold juice was strained through parachute silk to remove macro impurities, then shaken with ether; the penicillin would dissolve into the ether. The (heavier) water could then be drained off. Then the ether was shaken with alkaline water, and the penicillin would be back-extracted into the water. (Lax, 2004) Note that this process requires either a supply of or the ability to produce ether, a fairly volitile chemical.
  4. Stabilizing the penicillin in powder or crystal form.
In the coming days I will post separately about each problem.


Lax, Eric. The Mold in Dr. Florey's Coat: The Story of the Penicillin Miracle. Henry Hold & Company, New York: 2004. (An extremely readable, fairly popular history-of-science account of the discovery and production of penicillin, from Fleming to Florey. An excellent resource for stories associated with the problems of producing penicillin; see upcoming post about stories, human memory, and the distribution of this project.)

Herrell, Wallace. Penicillin and other Antibiotic Agents. W. B. Saunders Company, Philadelphia: 1945. (An account of what was known about penicillin in 1945, i.e., four years after the first purification of penicillin. Very useful for historical problems.)


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