Gordon Alles stands as a notable figure in pharmacology, whose work profoundly influenced modern medicine. His investigative approach to chemical compounds led to insights that reshaped therapeutic strategies.
Early Life and Scientific Pursuit
Gordon Alles, born on November 26, 1901, embarked on his academic journey at the California Institute of Technology (Caltech). He earned his Bachelor of Science degree in 1922, followed by a Master of Science in 1924, and completed his doctoral studies, receiving a Ph.D. in 1926. This comprehensive education provided him with a strong foundation in chemistry and prepared him for a career in pharmaceutical research.
Following his studies, Alles pursued a career that blended research with academic roles. From 1931, he served as a lecturer in pharmacology at the University of California Medical School in San Francisco. His academic career continued to evolve, and by 1951, he became a Professor in Residence of pharmacology at UCLA.
The Groundbreaking Synthesis of Amphetamine
In the late 1920s, Gordon Alles focused his research on finding an alternative to ephedrine, a natural compound used as a decongestant and bronchodilator for asthma. He aimed to synthesize a less costly and more easily produced substitute. This pursuit led him to investigate beta-phenyl-isopropylamine, a compound that had been synthesized by Lazar Edeleanu in 1887 but was previously considered without pharmaceutical value.
Alles’s work in 1927 involved independently resynthesizing this compound, which he later referred to as Benzedrine. His subsequent investigations were crucial, as he sought to understand its physiological effects. On June 3, 1929, Alles conducted a self-experiment, a common practice for researchers at the time, by having 50 milligrams of the substance injected into his own body.
During this self-experiment, Alles meticulously recorded his observations. Within minutes, he noted a clear nasal passage and a significant increase in his blood pressure. He also experienced heart palpitations, alongside a distinct “feeling of well being” and an unusual talkativeness. Although he found it difficult to sleep that night, with his mind racing from one topic to another, he considered the trial a success due to the observed physiological and psychological effects.
Medical Applications and Initial Impact
Following his initial observations, Gordon Alles recognized the stimulant properties of the compound, even though it did not prove to be a superior asthma treatment. He began sharing the substance with a select group of doctors and researchers for experimental use. This collaborative exploration led to the identification of several potential therapeutic applications for the newly characterized compound.
The earliest widespread medical application of amphetamine, marketed as Benzedrine, was as a nasal decongestant in an inhaler form by Smith, Kline & French (SKF) in 1932. Beyond its decongestant properties, the stimulant effects of amphetamine were soon explored for other conditions. It was found to be effective in treating narcolepsy, a sleep disorder characterized by excessive daytime sleepiness, and post-encephalitic Parkinsonism, a neurological disorder.
By 1937, the American Medical Association approved Benzedrine Sulfate tablets for these uses, as well as for mood elevation in certain depressive states. The drug also gained attention for its ability to reduce fatigue and enhance alertness, leading to its use by military forces during World War II to maintain wakefulness and focus in personnel. Additionally, its effects on appetite were noted, leading to its eventual use as a weight-loss aid.
Broader Contributions and Enduring Legacy
Gordon Alles’s scientific interests extended beyond amphetamine, encompassing a broader exploration of drug chemistry and its biological interactions. He conducted extensive research on insulin, investigating its isolation and properties for the treatment of diabetes. His work also delved into the properties of other compounds, including methylenedioxyamphetamine (MDA), which he explored in the 1930s and early 1940s.
Alles was particularly interested in the relationship between a compound’s molecular structure and its biological activity, a concept that underpins much of modern drug design. His inquiries included investigating the potential of alkaloids from the kava plant for developing tranquilizers and exploring medically useful compounds from cannabis. In 1958, his commitment to scientific advancement was further evidenced by a significant gift to Caltech, which largely funded the Gordon A. Alles Laboratory for Molecular Biology.
Alles’s enduring legacy is rooted in his pioneering work that bridged chemistry and pharmacology. His methodical approach to drug discovery and his emphasis on understanding structure-activity relationships helped shape the trajectory of pharmaceutical research. The impact of his initial characterization of amphetamine continues to be felt in therapeutic contexts, influencing the development of subsequent medications.