Modern Medicine

1. Introduction:
The journey of modern medicine has come a long way. Medical advances has improved lives and increased life expectancy from the early 20th century to present day. It wasn’t until the 1930’s and 1940’s where the production of sulfa drugs and penicillin (respectively) opened up a new horizon for the medical field. Many argue that medical advancements do not affect the decline of mortality, but rather the improvement in better living standards, better nutrition, public health improvement, and household hygiene are the main reasons why mortality had declined from the early 20th century to the mid 20th century (McKeown 1976). Using the research Journal called, “Modern medicine and the 20th Century Decline in Mortality: New Evidence on the Impact of Sulfa Drugs”, created by Seema Jayachandran (Stanford University and National Bureau of Economic Research), Adriana Lleras-Muney (UCLA and NBER), and Kimberly V. Smith (Princeton University), I will discuss the origin of sulfa drugs and how these drugs prospered over its few years of popularity in treating sick patients of infectious-bacterial diseases.

It was the first drug of its kind and was a cheap and efficient treatment available to pretty much anyone. I will also examine the later “wonder drug”, penicillin, through the U.S. Army Medical Department: Office of Medical History and a PDF published volume called, “Changes in the Age Distribution of Mortality over the Twentieth Century” (Author: David M. Cutler, Ellen Meara). Penicillin was a vital component to the allies of World War 2 and wasn’t exposed to the public until after the war. Though these drugs are different from each other and in the chemical make up, they would still accomplish the curing of an individual. Evidence through data tables and charts will help support and paint a clear picture of how sulfa and penicillin drugs during the 1937-1950-time period declined mortality rates. 2. Background

Sulfa Drugs
Some might say that sulfa drugs were considered the “first miracle drugs” or “magic bullets” to treat infectious diseases that were once considered deadly before the 1930’s. Common bacterial infections like staphylococcal (staph) and streptococcal (strep) were threatened as killers, but are now envisioned as easily curable diseases. In 1932, a German Scientist by the name of Gerhard Domagk was the first to develop a sulfonamides drug that was beneficial to mice with streptococcal; this drug was called Prontosil. It wasn’t until 1935 when Domagk’s work was published. This led to a major occurrence in 1936 at an England Hospital.

Prontosil was given to 38 female patients who all had a serious case of puerperal fever, which is caused by streptococcal infection at childbirth. The results showed a mortality rate of 8% for patients treated with Prontosil, and a mortality rate of 24% for the previous 38 patients with this infectious disease. Even though these results weren’t ground breaking, it was still the beginning of the sulfa drug era. Scientists knew they could expand the benefits and decrease mortality rates over time; whether that is in sulfa drugs, antibiotics, or penicillin.

Sulfa drugs entered the United States in 1935, and it didn’t take long before it became a huge medical hit. A variety of sulfa compounds were used to treat puerperal fever, pneumonia, scarlet fever, meningitis, gonorrhea, and erysipelas. Prontosil was first used in America in 1935 to treat a child with meningitis at Babies Hospital in New York. Johns Hopkins University and Western Pennsylvania Hospital; tested sulfa drugs as efficient treatments against scarlet fever and pneumonia. Pharmaceutical companies were crazed by the sulfa drug frenzy; in 1937 the sulfa drug output reached 350,000 pounds, by 1942 there were 5,000 sulfa drug companies who in total pumped out nearly 14 million pounds of sulfa drugs. The sudden increase in such a small time interval of sulfa drug treatment could may as well show a distinct analysis of the effects this drug had in the medical field and research studies, but would not be accepted as a true argument that sulfa drugs decline mortality directly. Today sulfa drugs are still being used, but are less used then antibiotics, which have a more effective treatment with less toxicity. Penicillin

Penicillin was a more potent medicine that was critically used for the troops who bravely fought in World War 2. Soldiers needed a quick efficient treatment to get them back on their feet. Penicillin was mainly used for sore throats, pneumonia, staph infections, and gonorrhea.

Sir Alexander Fleming was the first to discover penicillin in 1928. His findings were by accident; leaving a petri dish open with streptococcal bacteria exposed to the open air. He observed that the penicillin mold secretes an antibacterial substance that repressed the growth of the streptococcal bacteria. Fleming didn’t have the chemical recourses to further evaluate his findings, so in 1938 Dr. Howard Florey, a professor of pathology at Oxford University, took on Fleming’s discovery to improve and establish the drug we still use today. In 1940, Dr. Florey and his lab team infected 50 mice with streptococcus; half of the mice died, but the other half survived through the treatment of penicillin injections. At this point in time Florey was confident enough to apply penicillin to sick patients. He first treated a patient with slash wound infected with streptocci and staphylocci. Within five days the infection was gone.

Florey then took another giant step; in 1941, a little after the U.S. entered the war, Florey flew over to America to develop a means mass-producing of penicillin. This was quite necessary in aiding the troops over seas. In 1942, 400 million units of pure penicillin were produced, and by the end of the war pharmaceutical companies were producing 650 billion units a month.

Mortality rates would drop in American and British armed forces. According to a Journal called, “History of Infections Associated with Combat-Related
Injuries” written by Clinton K. Murray, Mary K. Hinkle, and Heather Yun; “Mortality from abdominal injuries decreased from 66% in World War 1 to 24% in World War 2.” This is a major improvement; penicillin was a miracle drug on the battlefield and becoming the ally’s most important weapon.

4. Results: I will briefly talk about the decline of mortality rates of sulfa drugs and penicillin; then I will explain each table and figure from the data in the analysis section. Sulfa Drugs: A regression analysis technique was used by researches to allow them to see if the trend breaks were larger for treatment diseases than for the control diseases, and to measure the magnitude of sulfa drugs on mortality. Also a difference-in-difference approach was used, comparing the mortality statistics (deaths per 100,000) of pre and post 1937 of treated diseases with pre and post of 1937 controlled diseases. The treated diseases consist of MMR (maternal mortality ratio), pneumonia/flu, and scarlet fever. The controlled diseases consist of tuberculosis and diphtheria.

Based on the research conducted by Jayachandran, Lleras-Muney, and Smith it was found that sulfa drugs were responsible for a 13% decline in pneumonia/flu mortality and a 39% of total mortality decline in this disease category. Sulfa drugs also resulted in a 25% decrease in MMR maternal deaths. The last of the treated diseases was scarlet fever, which had a 52% mortality drop from sulfa drugs. This accounts for 76% of total mortality decline for this disease between the pre-1937 and post-1937 periods. The mortality rate for maternal causes, pneumonia/flu, and scarlet fever were 1.1%, 10.5%, and 0.2% (respectively) before the pre sulfa drug period. This means sulfa drugs were responsible for 2% of overall mortality decline. This can be seen through table 1. 1. Table 1 presents two panels, Panel A (National mortality rates), and Panel B (Average state mortality rate).

This table supports data for sulfa drugs. Panel A: There is a mean and standard deviation for treated diseases and control diseases for 1920 to 1936 and 1937 to 1950. The 1920 to 1936 were the pre- sulfa drug era, which indicates that mortality rates were high. When data was gathered during the sulfa drug era (1937 to 1950), the mortality rates decreased by more then half. Panel B: The average state mortality rate had a very similar data trend as well. 2. Table 2 presents the difference in difference of the effect of medications on mortality. The diseases were analyzed in 2 intervals, 1915-1935 and 1945-1965. Pneumonia and influenza had a more rapid decline (-0.5%) then the dysentery, enteritis, and diarrheal disease (3.3%). The difference of the two diseases is –3.8%. This suggests that sulfa drugs and penicillin did have significant impact on mortality. 3. Figure 1 is a graph that shows the total mortality rate between 1920-1950. The break point indicated at 1937 shows the introduction of sulfa drugs; mortality rate steadily lowers from that point on.

4. Figure 2a shows the mortality trend of maternal mortality ratio (treated disease). This graph shows a more dramatic decrease in mortality. 5. Figure 2b shows the mortality trend of influenza and pneumonia (treated disease). This graph entails a decline in mortality at the start of 1937, with a couple of hiccups on the way. 6. Figure 3a shows the mortality trends for tuberculosis (controlled disease). The trend is overall declining before and after the introduction of sulfa drugs. 7. Figure 3b shows the mortality rate for diphtheria (controlled disease). The trend is similar to the controlled disease of tuberculosis. Diphtheria declined before and after the introduction of sulfa drugs. Penicillin:

I found interesting information off of the U.S. Army Medical Department website about penicillin attributes during the war; there was 3,986,221,000 units of penicillin administrated to troops. This is an astonishing number that blew my mind. Common wounds during World War 2 included wounds of the abdomen, chest injuries, head injuries, gunshot wounds of the spine, wounds of the buttocks, and burns. Respectively the mortality rate for each of these wounds is as followed: 14%, 6%, 10%, 2.8%, 2%, and 0.7% (Table 3). Death would occur when these wounds weren’t tended to by penicillin. Another type of disease greatly cured by penicillin was gonorrhea. This was a venereal disease unlike no other. In May 1943, 15 Army hospitals used to penicillin to treat 1,686 patients of gonorrhea. All the patients were men, and they were divided into several groups.

The dosage of penicillin varied form 100,000 to 160,000 units, 98% of the patients achieved a cure, while the others were given a lower dosage and were uncured. They were soon given the correct dosage amount and of the 126 re-treated 85 were cured of gonorrhea. Mortality rates were as low as any in military history (wars before WW2). 1. Table 3 shows the mortality rates during World War 2 of wound injuries. The highest number of deaths was 82 (wounds of the abdomen), but only had a mortality rate of 14%. The lowest number of deaths was from burns, which had a mortality rate of 0.7%. 2. Table 4 exploits data on the influence of antibacterial therapy on comparative case fatality rates in 1,526 abdominal injuries. By comparing penicillin and sulfadiazine treatment between 1944 and 1955 we can portray that penicillin was the more effective therapy. In 1944, of the 361 cases given sulfadiazine, 117 died (32.4% mortality rate).

In the same year, of the 727 cases given penicillin, 158 died (21.7% mortality rate). In 1945 zero patients were treated with sulfadiazine were given to patients with abdominal injuries. In that same year, of the 438 cases, 97 died (22% mortality rate). In total sulfadiazine usage gave a mortality rate of 32.4% (67.6 mortality drop) and penicillin usage gave a 21.8% mortality rate (78.2% mortality drop). 3. Figure 4 is a graph that shows the introduction of both sulfa drugs (between 1935-1940) and penicillin (1940 to 1945). When sulfa drugs come into play there is a slight decrease in mortality, but when penicillin is introduced there is a more dramatic fall in mortality. *This does not relate to the main topic of World War 2, but it does give you a large overview of how penicillin has affected the maternal mortality rate. 4. Figure 5 is similar to figure 4, but goes in more detail. Three age groups are considered: infants, elderly, and age-adjusted. The graph displays the introduction of sulfa drugs and penicillin, and how these therapies affected the mortality of pneumonia and influenza.

For infants the mortality rate before the introduction of sulfa drugs was sporadic, but after 1935 dropped. When penicillin was first used the mortality rate continued to drop, but not as drastically. For the elderly, mortality declined sporadically, having some ups and downs, before the sulfa drug discovery. When sulfa drugs were introduced the mortality rate declined, but declined even more when penicillin was first used. Age-adjusted shows a steady decline in mortality for both the introduction of sulfa drugs and penicillin. *Yet again this figure does not relate directly to the main topic of World War 2, but instead shows the promise penicillin had during the 20th century.

5. Conclusion

Sulfa drugs and penicillin didn’t drastically decline mortality rates during the 1937-1950 era, but they sure did open a new horizon to the up and coming medical advances. These drugs were the founding fathers of the pharmaceutical revolution; people had an accessible way of getting treatment of infectious diseases that would sometimes lead to death. Pharmaceutical companies benefitted and aided to the soldiers who fought in World War 2.

Reminiscing on some results, we can see that the introduction of sulfa drugs resulted in a maternal mortality rate drop of 25%, a 13% drop in pneumonia and influenza mortality, and a 52% drop in scarlet fever mortality. Penicillin effects during World War 2 had similar, but great effects. In 1944-45 data was collected for the deaths from bacterial peritonitis and peritoneal contamination. The mortality rates after sulfadiazine usage was 32.4% (67.6% mortality drop), and for penicillin usage the mortality rate was 21.8% (78.2% mortality drop). Finally the overall average mortality rate of wounds from World War 2 was 4.25% (Table 3).

All in all, the research found on these drugs definitely had an overall positive effect on mortality rate. If they didn’t then they wouldn’t exist in today’s day and age. Everyone has been prescribed these drugs from time to time, and for me to understand its origin and success rate when it was first introduced is pretty interesting and amazing.