Monday, October 3, 2016

1950: The discovery of steroids

Now in our quest through the annals of history, we come to steroids. If we consider the discovery of epinephrine the most significant to our asthma history, then the discovery of steroids must be a close second.

While epinephrine was isolated in 1901 from the adrenal medulla, cortisol wasn't isolated until 1936. However, interestingly, the history of both substances can be traced back to 1714, when Eustachius described the adrenal gland.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1760737/

However, the story of steroids probably began in 1849, where Thomas Addison, working for Guy's Hospital in Britain, was looking to learn more about diseases and define them for the medical community. This quest lead him to making the link between Addison's Disease and the Adrenal Gland, and then to define the disease that would eventually take his name.

This discovery lead to further research on the adrenal gland. In 1894, researchers isolated a hormone from the adrenal cortex that they referred to as "cortin." In 1900 Solomon Soles-Cohen, working for Jefferson Medical College in Philadelphia, described the benefits of using adrenal extracts in asthmatics.

http://jama.jamanetwork.com/article.aspx?articleid=477214
Jackson, Mark, Asthma: A Biography," 1989,

Then, in 1901, researchers isolated a hormone call epinephrine from the adrenal medulla. The significance of cortin was not immediately recognized. However, the significance of epinephrine was recognized, and it was soon learned to have end asthma attacks, and this spearheaded a quest that lead to our modern understanding of asthma.

So, despite all that, the significant portion of the history of steroids, the part that is most recognized by historians, begins in the mid 1930s. And it did not begin with asthma in mind: it began as part of a quest to find a treatment for rheumatoid arthritis.

It began when Dr. Philip S. Hench, who was working for the Mayo Clinic. During the 1930s he observed that pain symptoms subsided during pregnancy and jaundice. His theory was that this was the result of increased cortisol levels. (1, 2, 3)

Hench believed a "substance x" was produced by the adrenal gland in response to stress, and that it would reduce inflammation in joints that occur in people with rheumatoid arthritis, a disease associated with pain in the joints due to chronic inflammation.

Beginning in 1935, this lead him to performing experiments with Edward C. Kendall at the Mayo Clinic to isolate the compound in the adrenal cortex. (1)

In 1936, Kendall succeeded in isolating compounds from the adrenal gland, and he named them in the sequence they were discovered: compound A through F.  Upon further research, he realized that compound E and substance X were one and the same. Hench named this substance cortisone. (2, 4)

In 1943 they extracted cortisone from the adrenal gland for clinical trials. And in 1944 they injected it into a patient with rheumatoid arthritis. They described how this patient was able to walk up and down stairs without discomfort. (1)

In 1948, Tadeus Reichstein, a Polish born chemist, perfected the method of extracting adrenal hormones, and this opened the door for further research. So Kendall and Reichstein had succeeded in isolating cortisol, and then Adrenocorticotropic hormone (ACTH).

That same year, a man was given cortisol as a treatment for rheumatoid arthritis. This was synthetic cortisol, making the medicine readily available for experimentation.

In 1949, a report was released in Mayo Clinic Proceedings showing the benefits of cortisol for the treatment of arthritis. (2)

It was described as the "miracle cure." In 1950, for their work in this great discovery, Kendall, Hench, and Reichstein were awarded the Nobel Prize for Physiology in Medicine.

This inspired researchers to study the affects of cortisol on various diseases, including asthma and allergies. At the time it was believed inflammation was part of the inflammatory response, although it was not known that some degree of inflammation was chronic. This discovery would not be made for another 30 years of so.

In the meantime, cortisol was hailed as a miracle cure, and was prescribed liberally. This was despite knowledge that it caused side effects, such as fluid retention, moon face, acne, and depression.

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