This post is part 2 of a series.
in a.d previous blog, I described the development of World War II psychopharmacologyUsing the examples of Frank Berger (creator of meprobamate) and Heinz Lehmann (promoted the clinical use of chlorpromazine). In this post, we’ll describe how World War II nuclear weapons research played a role in the development of the inhalation anesthetic halothane, and then conclude with comments on the war’s connection to both. neurology and psychopharmacology.
The discovery of halothane
By the 1930s, the limitations of ether and chloroform, discovered almost a century earlier, became increasingly apparent, as did the agents designed to replace them. Thus, there was a great need for safer and more effective anesthetics. How this happened takes us to the story of Charles W. Suckling (1920-2013). Born in Middlesex in southeast England, he inherited a family tradition of explosives chemistry. His maternal grandfather and uncle both worked in gun cotton production at Alfred Nobel’s factory in Ardeer, Ayrshire, and later at the Royal Ordnance Factory in Waltham Abbey, Essex, where his paternal grandfather also worked.
In 1939, he entered the Faculty of Chemistry at the University of Liverpool. In the early years of the war, the Liverpool area was heavily bombed; Although Suckling’s future wife was not injured, she was “bombed” twice. He assisted his brother Ted as a fireman, and in one memorable incident, the brothers proudly entered the shelter and displayed the still-hot fragments of an exploding incendiary bomb; immediately reprimanded by his mother.
After graduation, the Ministry of Labor and National Service ordered Suckling to work for Imperial Chemical Industries (ICI), a large company engaged in the production of war materials and pharmaceutical products at the time. By the way, he had a lot of experience with the chemical element fluorine halogen, which is in compounds for aerosols and refrigerants; therefore, Suckling was assigned to the Tube Alloys project, the code name for Britain’s covert effort to develop the atomic bomb. At that time, emphasis was placed on the process of enriching uranium-235 yield. This “yellowcake” involved turning uranium powder into a gaseous compound containing fluorine, which could then be separated from the U-238 in a centrifuge. It was during this research that Suckling developed skills in fluorine chemistry that later served him well in civilian life. Meanwhile, in his off-duty time, he served in the Home Guard and survived the explosion at the Tube Alloys facility in Merseyside, where work was quickly restored.
After the war, Suckling completed his doctorate and returned to ICI in 1949. At that time, there was great interest in finding applications for the new knowledge of fluorine chemistry. Both of them management The Manhattan Project and the Mallinckrodt Company funded research on the development of anesthetics, but did not yield positive results. Nevertheless, one of Suckling’s bosses, John Ferguson, was interested in the problem and in 1951 encouraged him to take up the work.
Suckling knew that adding halogens to organic compounds reduced their flammability and that fluorine in particular caused them to evaporate more easily. By 1953, he had created halothane, which can be considered a derivative of ethane, containing fluorine and other halogens such as bromine and chlorine. It is easily vaporized and appeared to anesthetize insects and animals. The promising compound was submitted by ICI to the Anesthesia Group at Oxford for further study.
As soon as anesthesiologists at Oxford adopted halothane, they had a long history of pioneering drugs and treatments. They used it about 40 times on their own before they were sure it was safe to give to patients. After a series of systematic clinical studies, they published an article in a journal British Medical Journal; halotan soon hit the market.
Halothane was not flammable or a respiratory irritant, but it also had limitations, including liver damage. It is no longer on the market in the US and will be replaced by later related compounds. But his history is important, because he was one of the first examples of “rational pharmacology”, that is, the creation of drugs based on the knowledge of the physiological effects of various chemical structures.
War as an impetus for discovery
Just as the wartime experiences of discoverers were variable, so was the extent to which the needs of war stimulated neuroscience and pharmacology. The post-war clinical development of chlorpromazine (another example of the use of halogen chemistry) and lithium was carried out in military hospital settings, but by independent individuals and not as part of an organized war effort (1). This also happened in other areas of pharmacology, for example, the study of mustard gas as a chemical weapon led to the development of the first cancer chemotherapeutic drugs – nitrogen mustards.
Basic Readings in Psychopharmacology
In recent years, some have worried about what they see as the “militarization of neuroscience,” pointing to modern research into mind-controlling weapons or the use of MRI for “brain fingerprinting” to search for terrorists at airports (2). Others argue that neuroscience has always had both military and civilian roots, pointing to the role of facilities such as the Walter Reed Army Institute of Research (3).
In summary, some discoveries were made through organized war programs, while others were the unplanned results of technologies developed for other purposes during the war. In other cases, military hospitals provided the conditions people were chasing goalsit was not specific to military operations. Sometimes the clinical experience of wartime medicine influenced thinking that led to later discoveries or projects such as the Paralympic Games (4). In other cases, the necessity of military service delayed research until after the war.
During the war, neuroscience and psychopharmacology did not have a single way of development. In a sense, it feels like an organic process influenced in various ways by the environment and the personalities of the people involved. And, of course, one can guess how many innovations were not implemented because their potential inventors did not survive.
