Monday, May 14, 2012

Penicillin and the Importance of Medicines From Nature

Medicines from nature vary from using a single naturally occurring substance as an active ingredient to using an entire organism in pharmaceutical drugs. Specimens for medicinal research range from little tiny microbes to organs of animals bigger than us. Some examples being insulin derived from the pancreas of pigs or cattle, chemotherapeutic agents from plants, and the one I’ll be focusing on today, antibiotics from microorganisms such as Penicllium. There’s no estimation on where the human race would be today without the help of our environment and the things living all around us.

            Penicllium Notatum, a rare strain of Penicllium, is able to produce and secrete a chemical called Penicillin G. It was first discovered by a French Medical student, Ernest Duchesne in 1896 but no further research was performed due to its instability. It wasn’t until one day in September of 1928, when Alexander Fleming observed a bacterial zone of clearing around the mold of Penicllium that demonstrated it as a possible antimicrobial agent. The research of Penicillin G was reopened and the drug that we all know of today as Penicillin cured its first human from a life threatening infection in 1941.

            After this first human trial run, came the question of how they were going to produce Penicillin on a large scale. Scientists tried many different mechanisms to increase yield ranging from UV induction to addition of Penicillin precursors. In the end, Pfizer opened its first commercial plant for large-scale production in March of 1944. Their method of mass production included fermentation with corn steep liquor and constant aeration, recovery, and freeze-dry purification. By the end of that same year, Penicillin was the primary disease preventing drug used in the military and much of the United States. And just a year later, in 1945, Alexander Fleming and colleagues involved in the research of Penicillin was awarded the Nobel Prize.

            So you might be asking now, how does such a small and insignificant organism be caught in such a momentous achievement of medicine? And its because Penicllium Notatum have evolved this way that allows for it to kill off all surrounding bacteria for food, and this is by Penicillin G. Penicillin G is secreted during times of nutrient deprivation to prevent the growth of bacteria in its surroundings. It does this by inhibiting the enzyme, transpeptidase, which is responsible for the structure and strength of the bacterial cell wall. Without transpeptidase, when water rushes in, the wall is unable to withstand the pressure, resulting in a ‘lysis’, or a cell burst. 


            In the image below, is a time lapse photograph taken of the development of Chlamydia Trachomatis in the absence (A) and presence (B) of penicillin. You can see that in strain B, the infectious reticulate bodies have been enlarged to the point where they are no longer in an infective state.



And in the video below, is another time lapse of penicillin working its way to cell lysis. 

video

Penicillin is able to disrupt the synthesis of cell wall with the process discussed and shown above in numerous disease-causing pathogens such as streptococcus, staphylococcus and virtually all pathogens. It was virtually all pathogens until bacteria started being able to grow resistant to Penicillin. This occurs when a mutation in a bacterial strain allows for resistance against Penicillin G, which therefore allows them to out compete wild type strains. In cases like this, stronger and more potent Penicillin must be created. And this is widely known as the Antibacterial Arms Race. Since the original Penicillin, other similar antibiotics have been discovered and created such as Penicillin V, Ampicillin, Methicillin, etc.

            Since the discovery and commercialization of Penicillin back in the 1940s, pharmacologists from all over the world have been able to derive naturally occurring substances in organisms and use them for disease prevention. And now, not only disease prevention, but also antidepressants, healing, and much more are being derived from natural sources and being used to help humans. For example, an entire field called herbalism, termed as the practice of plants as medicine to restore human health and wholeness. Another example being a natural antidepressant extracted from a golden flowering plant called St. John’s Wort. This last example, being a little far fetched, is expressed by Paul Stamets, on how mushrooms of this world can someday save the entire planet. 



          Penicillin is just one example of many on how we are able use a provisioning ecosystem service from nature that benefits human health and well being. As in just the provisioning spectrum of ecosystem services, there are still the other 3 categories of services that the ecosystem provides for us. Its no wonder why biological diversity is so important. Not only does it benefit the environment and countless number of other species, but also more importantly, we, as a whole absolutely need biodiversity to survive. Without it, we wouldn’t be where we are with our medical advancements, genetic advancements, etc.


Works Cited:

Corey Atteridge and Mark Tromblay. Penicillin: Structures and Functions. Middlebury College. January 1997.

Discovery of Penicillin. American Chemical Society. 2012

Time lapse image and video provided by:
Rachel J. Skilton,et al. Penicillin Induced Persistence in Chlamydia trachomatis: High Quality Time Lapse Video Analysis of the Developmental Cycle. PLoS ONE 4(11). 20091

TED talk:
http://blog.ted.com/2008/05/06/paul_stamets/


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