Lisa Wong

Julius Axelrod – 1970 Nobel Prize in Medicine or Physiology

You see people plagued by this on the streets, sitting next to you on the subway, or sometimes even at your bedside. Mental illnesses affect one in four people worldwide (“Mental Health” 2). For these people, Prozac, Zoloft, Paxil are all common names of medications that they take in order to take hold of their lives. Prior to the findings of Julius Axelrod (1912-2004), recipient of 1970 Nobel Prize in Medicine or Physiology, mental illness was perceived as an affliction of your feelings and surroundings (“Julius Axelrod Papers”).  Not only did his work lead to our understanding that mental illness is actually a medical problem, but it also led to the creation of selective serotonin reuptake inhibitors (SSRI’s), which help alleviate this problem.

Although Axelrod worked independently, he shared the Nobel Prize with Swedish physiologist Ulf Von Euler and biophysicist Bernard Katz (“Julius Axelrod”). In fact, the research that he won the award for was built upon the findings of Ulf Von Euler. Euler discovered a neurotransmitter called norepinephrine (also called noradrenaline). Norepinephrine is one of the body’s main neurotransmitters. An excess of it can make you feel anxious and fearful, which is likely the case for those suffering from anxiety disorder or panic attacks. However, a deficiency of it can make you lack energy and motivation, or be depressed. Building on top of Euler’s research, Axelrod discovered that norepinephrine can be inactivated by an enzyme that he identified as catechol-O-methyltransferase (Wrobel).

In the 1950’s, scientists believed that neurotransmitters – chemical messengers used as signals in the nervous system – simply stopped working after they were released by nerve cells and broken down by enzymes. Axelrod thought the same too. During the time, a popular type of antidepressant drug was monoamine oxidase inhibitors (MAOI’s), which works by disabling the enzyme monoamine oxidase that interferes with the actions of neurotransmitters. He believed that this enzyme broke down the neurotransmitter norepinephrine after it was released by the nerve cell (Wrobel). During the experiments of one of his fellow scientists, it was found that even after the enzyme monoamine oxidase was stopped, somehow, norepinephrine was still interfered with. This meant that norepinephrine was removed from the system in some other way (Wrobel). In an experiment in which Axelrod injected radioactive norepinephrine into lab animals, he could clearly see that they went to organs rich in sympathetic nerves, like the heart or spleen. However, he wanted to know where the neurotransmitters went in terms of nerve cells.

Since it was not possible to visibly see where they went at the time, he devised an experiment in which he first gave lab animals MAOI’s to make sure the monoamine oxidase enzyme would not interfere with the norepinephrine. Next, he disabled the sympathetic nervous system on one side of the animals’ body and lastly, gave them the radioactive norepinephrine. He found that on the side where the sympathetic nerves had been disabled, there was not any radioactive norepinephrine. However, on the other side where the nerves were still intact, there was clear evidence of radioactive norepinephrine. It became apparent that the reason that norepinephrine was inactive was because it was absorbed into the sympathetic nerves. With these findings, Axelrod revealed that neurotransmitters aren’t always released by nerve cells and broken down by enzymes. They are also involved in a system called reuptake in which they are recaptured by the nerve cell that released them so that they can be used again when necessary (Iversen).

Axelrod’s discoveries completely revolutionized our understanding of the way that medications and illnesses work. We came to realize that the mental state is a result of some complicated chemistry and physiology. His discoveries led to what generally was a more comprehensive understanding of what drugs do to the brain. For instance, scientists were able to figure out that cocaine prevents the reuptake of both norepinephrine and dopamine (a neurotransmitter that is associated with pleasure) back into the nerve cells. Thus, there becomes a large amount of these neurotransmitters associated with stimulation and pleasure, causing a temporary high. It also ushered in an age of pharmacology in which drugs were designed to either inhibit or stimulate neurotransmitters in the nervous system (“Julius Axelrod Papers”). Most notably, it changed how we treat mental illnesses such as depression and anxiety. The new concept of reuptake made it possible to design a drug that would selectively focus on one neurotransmitter – SSRI drugs in particular (Wrobel).

SSRI’s are antidepressants that essentially stop the body from reabsorbing a chemical called serotonin, which is thought to maintain our mood (McIntosh).  An imbalance of it can cause depression. In other words, SSRI’s increase the amount of serotonin neurotransmitters in our body, thus elevating our mood. Prior to Axelrod’s discoveries and the subsequent creation of SSRI’s, less efficient categories of antidepressants such as tricyclic antidepressants (TCA’s) and monoamine oxidase inhibitors (MAOI’s) were used. Although SSRI’s still have adverse side effects, they aren’t nearly as severe as those of TCA’s and MAOI’s (Smith, et al). They are also safer to overdose on, if that is ever the case, because they actually target a specific chemical, instead of changing the flow of many (Wrobel).

Julius Axelrod helped lay the foundation for understanding the mechanics of our minds. His investigations about norepinephrine and reuptake led to our modern understanding of how nerve cells in the brain regulate mood and behavior. Despite not possessing the equipment necessary to pinpoint the location of neurotransmitters, Axelrod showed innovation in creating an experiment that got past such an issue. The science that many of us view so distantly is actually closely the reason a fourth of the world’s population can lead more stable lives. It led to the most commonly prescribed class of antidepressants – SSRI’s – to date (McIntosh). Axelrod’s efforts changed a long history of blaming illnesses on the efforts of the afflicted. Quite remarkably, an emotionally burdensome stigma has been has been scrapped and replaced by an understanding that sufferers of mental illnesses can’t just “snap out of it.”

Works Cited
“Axelrod, Julius – Complete Dictionary of Scientific Biography.” Encyclopedia.com.
Charles Scribner’s Sons, 2008. Web. 3 Oct. 2014.
http://www.encyclopedia.com/doc/1G2-2830905455.html

Iversen, Leslie. “Obituary – Julius Axelrod.” Catecholamine Society. University of Oxford. PDF.
“Julius Axelrod.” Encyclopædia Britannica. 2014. Britannica Online. Web. 6 Dec.. 2010.
http://www.britannica.com/EBchecked/topic/46108/Julius-Axelrod
“Julius Axelrod.” Jewish Virtual Library. American-Israeli Cooperative Enterprise, 1 Jan. 2014. Web. 3 Oct. 2014. <https://www.jewishvirtuallibrary.org/jsource/biography/axelrod.html>.
“Julius Axelrod – Facts”. Nobelprize.org. Nobel Media AB 2014. Web. 4 Oct 2014.<http://www.nobelprize.org/nobel_prizes/medicine/laureates/1970/axelrod-facts.html>.
“Julius Axelrod – Nobel Lecture: Noradrenaline: Fate and Control of Its
Biosynthesis”. Nobelprize.org. Nobel Media AB 2014. Web. 4 Oct 2014. http://www.nobelprize.org/nobel_prizes/medicine/laureates/1970/axelrod-lecture.html
McIntosh, James. “What is serotonin? What does serotonin do?” MNT. Medical News Today, 1 Sept 2014. Web. 5 Dec. 2014. http://www.medicalnewstoday.com/articles/232248.php
“Mental Health 2013: An Important Public Health Issue.” NAMI-GC. 2013. Web. 5 Dec. 2014. <http://www.namigc.org/wp-content/uploads/2013/01/MentalIllnessFactSheet-July-2013.pdf
Rubin, Ronald P. “A Brief History of Great Discoveries in Pharmacology: In Celebration
of the Centennial Anniversary of the Founding of the American Society of Pharmacology and Experimental Therapeutics.” Phamocological Reviews. American Society for Pharmacology and Experimental Therapeutics, Dec. 2007. Web. 3 Oct. 2014.
Smith, Segal.” Types of Antidepressants and Their Side Effects” Help Guide. Nov 2014. Web. 5 Dec. 2014. http://www.helpguide.org/articles/depression/types-of-antidepressants-and-their-side-effects.htm

Squire, Larry R. “Julius Axelrod.” The History of Neuroscience in Autobiography. Vol. 1. Washington, D.C.: Society for Neuroscience. 1996. PDF.
“The Julius Axelrod Papers-The Nobel Prize and Public Science after 1970.” Profiles in Science. National Library of Science. Web. 3 Oct. 2014.

Tucker, Anthony. “Obituary: Julius Axelrod.” The Guardian. Guardian News and Media Limited, 30 Dec. 2004. Web. 3 Oct. 2014.<http://www.theguardian.com/news/2004/dec/31/guardianobituaries.health>.

Wrobel, Sylvia. “Science, serotonin, and sadness: the biology of antidepressants.” The FASEB Journal. Fedearation of American Societies for Experimental Biology, 2014. Web. 5 Dec. 2014. http://www.fasebj.org/content/21/13/3404.full