Searching for The Ability to Remember as Depicted in Rick Riordan's Novel, The Son of The Neptune

The discovery of penicillin in 1929 marked the beginning of the modern antibiotic era. Penicillin’s influence on modern medicine was immense, proving effective in curing previously fatal diseases, such as scarlet fever and syphilis, and giving rise to the antibiotic industry. However, though its antibiotic potential was immediately evident, large-scale production and clinical testing were not in effect until the onset of World War II. The immense military casualties and the spread of sexually transmitted diseases among soldiers of World War II created a demand for penicillin. Thus, the demand created by World War II for an antibiotic incited an international effort between the United States, England, and Canada to expedite the mass production and clinical testing of penicillin.

Penicillin was first discovered in 1929 by Alexander Fleming at St. Mary’s Hospital, London. Fleming observed that a spore of mold contaminated a petri dish containing Staphylococcus, thus inhibiting the organism’s growth. Upon further research, Fleming recorded that the mold of Penicillin notatum could dissolve staphylococci microbes, thus resulting in the emergence of the antibiotic penicillin. However, two major obstacles prevented the immediate widespread usage of penicillin upon discovery. Penicillin had to be administered intracutanesouly or intravaneously in a series of injections as close as possible to the infected area, because oral ingestion proved ineffective. Because penicillin is excreted from the human body at such a rapid rate, adequate concentrations of the antibiotic would have to be maintained in order for effective usage. However, at the time of Alexander Fleming’s discovery there was no economical method to mass-produce the mold. Thus, despite the immense possibilities associated with Fleming’s discovery, penicillin production and research remained dormant. In fact, “were it not for the war, it is mostly likely that [penicillin] would still be little more than a laboratory curiosity”(Elder).

World War II ignited the penicillin craze in England. In 1939, Dr. H.W. Florey headed an Oxford team in renewing and reviving the immense potential of penicillin as a war-time drug. The first real support from outside England came in 1941 when a Rockefeller grant of five thousand dollars was made to support the progress of Dr. Florey’s work. However, as conditions rapidly deteriorated in England due to the ongoing war, Dr. Florey and his associate, Dr. N.C. Heatley, were forced to visit the United States and share their studies so that the advancement toward an antibiotic could continue on safe soil.

The Office of Scientific Research and Development oversaw the initial work on penicillin in the United States. The transition from primarily English to American research marked a key moment in penicillin’s development, because prior to Dr. Florey’s decision to share his research in hopes of accelerating the process, the United States’ contributions to the penicillin effort were minimal, as evident by the meager grant awarded to Foley by the Rockefeller foundation. Had Dr. Foley not included the United States in the development of penicillin, England’s diminishing funding and resources due to World War II could have stunted penicillin’s advancement, thus leaving thousands of soldiers to die of treatable infections of penicillin. Because the demand for penicillin for World War II was increasing, the penicillin project turned international through Dr. Foley.

The United States played the most significant role in the production of penicillin. Dr. Robert D. Coghill of the Fermentation Division of the Northern Regional Research Laboratory, a research facility of mold cultures founded in 1940, fathered the production of penicillin in the United States. Dr. Coghill was one of those contacted by Dr. Florey upon his visit to the United States. His research team, competent in the field of fermentation, undertook the challenge of increasing the yield and recovery in the production of penicillin. First investigated by French microbiologist Louis Pasteur in 1860, fermentation refers to the process by which large organic molecules are broken down into smaller molecules. Thus, the science of fermentation had been available for some time prior to Dr. Coghill’s encounter with penicillin. However, the process of fermentation at its current state did not provide enough yield to prove effective, because not only was there an increasing demand for the drug but penicillin quantities must be maintained within a patient due to the rapid excretion of the drug. In response to this dilemma, Dr. A.J. Mayer, a co-worker of Dr. Coghill, discovered that the yield of the mold increased tenfold with the addition of corn steeping liquor to the liquid on which the mold grew. Within a short period of this discovery, “the yield had increased from two up to forty Oxford units per cubic centimeter”(Elder).

Soon after this advancement in penicillin yield, the Drugs and Cosmetics Section of the Chemicals Division of the War Production Board assumed responsibility of the accelerating production. The War Production board evaluated three primary methods of production: the trickle process, the surface process, and the submerged process. The trickle process involved pouring inoculated concentrate over stones or wood under sterile conditions so that the mold would adhere to the surfaces while the liquid continued to flow. This method proved to be too expensive for practical production. Surface process involved growing the mold on the surface of a medium under sterile conditions. This process resulted in good yields, however the long growing cycles and expensive equipment made the process unsuitable for mass production. Finally, the submerged process entailed aerating the mold for several days as it grew in the broth. Upon the conclusion of the fermentation cycle, the penicillin was removed from the broth and the mycelium was discarded. This was the most effective and economical production method as it produced high yields at a relatively low cost.

The results of these method experiments were astronomical. The combination of more efficient fermentation and increased development of production plants escalated penicillin manufacturing. By 1944, the United States War Production board had funded the completion of eighteen manufacturing plants. Production of penicillin began at 0.4 billion units in June of 1944, and increased exponentially to 0.7 in July, 0.8 in August, 1.7 in September, 2.8 in October, 4.8 in November, and 9.1 in December (Florey). These production statistics highlight the immediate positive effects of the War Production Board’s funding and leadership. The necessity of penicillin for armed forces during World War II was recognized by the Drugs and Cosmetics Section of the Chemical Department, thus, the leadership of the War Production Board incited an acceleration to improve the fermentation process of penicillin in effort to successfully mass produce the mold.

The production of penicillin to quench the demand of armed forces in World War II was promoted to an international scale in 1943. Prior to 1943, manufacturing of penicillin was limited to the United States due to its accessibility of funding, equipment, and research. However, in August of 1943 the Canadian Federal Government exhibited interest in establishing production plants in Canada to assure that the Canadian armed forces had access to the antibiotic. Similar to the research conducted in universities in the United States, Canada began funding Dr. Philip Greey to undertake studies of penicillin in the Department of Pathology and Bacteriology of the University of Toronto. The United States’ aided Canada’s efforts greatly. As a result of cooperation between the Canada’s Federal Government and the United States, the War Production Board released Dr. Coghill’s research to Canada and provided essential equipment for the plants. The collaboration between the United States and Canada was so effective that by August of 1943 large-scale production began in Montreal and Toronto. By 1944, Canada possessed three production plants.

Canada’s involvement in World War II provoked this effort to join the United States in the mass production of penicillin. To combat the increasing brutality of the war and decrease infection rates among injured soldiers, Canada turned to the United States for aid and mentorship. Thus, World War II was responsible for prompting an international cooperation, which led to increased research, the establishment of production plants, and ultimately expanding the influence of penicillin in the 1940s.

In addition to the military’s demand of penicillin as an infection preventative for injured soldiers, World War II presented the United States with a novel demand. Beginning in 1940, U.S. medical researchers were charged with the challenge of combating the spread of Sexually Transmitted Diseases among soldiers who contracted the diseases from prostitutes. Though studies of the effectiveness of penicillin against STDs were limited, the United States military began utilizing penicillin as post-STD exposure treatment due to its ability to prevent syphilis symptoms. Due to this new military demand for penicillin and the lack of research encompassing penicillin as a prophylactic drug against STDs, the United States began investing funds to conduct clinical studies.

The first major experimentation of penicillin was conducted in Terre Haute, Indiana in 1943. Researchers attempted to infect consenting prisoners at the penitentiary in Terre Haute with gonorrhea. However, the Terre Haute Prison Experiment ultimately failed to infect enough inmates with gonorrhea to obtain reliable results. Thus, the effectiveness of penicillin against STDs remained inconclusive, prompting the United States to fund another larger experiment.

Based on the Terre Haute experiment, the Guatemala Syphilis Experiment was conducted from 1946 to 1948. This American medical research project on penicillin was widely recognized for its unethical experimentation and techniques on the vulnerable population of Guatemala. Unlike the Terre Haute experiments, this study was intended to determine the effectiveness of penicillin in treating and preventing the symptoms of syphilis and the population tested was vastly larger. The Guatemala Syphilis Experiment infected and tested “more than 5,500 Guatemalan prisoners, sex workers, soldiers, children, and psychiatric patients, about one-quarter of whom were deliberately infected”(“Guatemala syphilis experiment”).

The Guatemala Syphilis Experiment, directed by United Sates public Health Service scientist Dr. John C. Cutler, was funded by a grant from the United States National Institute of Health to the Pan American Sanitary Bureau and the Guatemalan government. In need of a center for research, the United States funded the construction of a 300-bed hospital in Guatemala City. This city was selected due to its high population of possible test subjects, including prostitutes, soldiers, prisoners, and mental hospital patients. As a result of negotiations between the Guatemalan government and Pan American Sanitary Bureau, the United States research team was granted access Guatemalan public health records, orphanages, mental institutions, and hospitals to collect test subjects.

Approximately 1,308 subjects from 10 to 72 years of age were intentionally infected with STDs (“Guatemala syphilis experiment”). In the initial stages of the experiment, female commercial sex workers were infected with syphilis, and then instructed to engage in unprotected intercourse with unknowing soldiers and inmates. The spread of syphilis through this channel resulted in a population of unknowing and non-consenting victims. However, this effort to allow the disease to spread naturally failed because, like the Terre Haute experiment, not enough men contracted the disease. In response to this obstacle, researchers shifted strategy to the direct inoculation of soldiers, inmates, and mental hospital patients. Sex workers were infected with syphilis through the inoculation of the cervix. Prisoners were infected through direct injection or intercourse with previously infected sex workers. Finally, mental hospital patients were inoculated through direct injection, abrasion to the penis, oral ingestion, or cisternal puncture, which is the insertion of a needle to the back of the skull.

To analyze the effectiveness of penicillin, 5,128 patients underwent a series of serology tests (“Guatemala syphilis experiment”). Serology tests involved collecting blood and spinal fluid samples from subjects, and analyzing the samples for microorganisms and antibodies indicative of infection. Of those tested, 820 subjects received treatment through penicillin. Fewer antibodies represented greater effectiveness of the administered penicillin. The results indicated that the oral ingestion or direct injection of penicillin was an effective prophylactic against syphilis.

Both the Terre Haute Experiment and the Guatemala Syphilis Experiment originated due to the spread of STDs through the United States military forces during World War II. The necessity for a preventative incited the emergence of clinical studies under the direction of the United States. Though the Terre Haute research was inconclusive due to difficulties in infecting the patients, the Guatemala experiments provided vital evidence for the effectiveness of penicillin against syphilis. However, The Guatemala Syphilis Experiment also brought about a host of ethical violations. For example, the United States sponsored research on a highly vulnerable population without formal consent from many of the study subjects. The infection techniques utilized were extremely brutal and deceptive. Those who were subject to direct infection underwent painful processes, such as abrasions to the penis. Additionally, much of the population was infected through sexual contact without knowledge. As a result from the experimentation in Guatemala, at least 83 people were reported to have died during the research. The necessity for penicillin to protect the military against the spread of STDs was so great that the United States undertook these clinical studies despite their evident ethical violations.

World War II fathered penicillin from its discovery by Alexander Fleming to its mass production worldwide, ultimately giving rise to the antibiotic industry. Wounded and infected soldiers created a necessity for penicillin, resulting in an international effort to mass-produce and test the drug. England and the United States assumed the greatest responsibility for the research and discovery of penicillin, while Canada and the United States collaborated closely to perfect fermentation methods and increase production yields. Additionally, the United States enacted two large-scale studies of penicillin against syphilis, the Terre Haute Experiment and the Guatemala Syphilis Experiment. Despite their ethical implications, these studies were vital to the success of penicillin. In conclusion, World War II created a demand for penicillin, which resulted in an international effort to maximize production and implement clinical studies.