Restoring and Regulating the Body’s Biochemistry
In the early 20th century, scientists made great strides in understanding the roles of the body’s own chemicals in regulating its functions and transmitting information among its parts. Among these chemical substances were enzymes, hormones, neurotransmitters, and histamines. Since many diseases were thought to be caused by some sort of imbalance in the body, it seemed obvious to researchers that assisting or interfering with these substances ought to provide treatments for many maladies. The second half of the century built on these early investigations and ideas and ushered in the era of rational drug design. Whereas, historically, drug developments often resulted from trial and error, the principles of rational drug design were based on a deeper understanding of the body’s biochemistry and involved designing molecules with specific molecular structures to interact with biochemical processes in specific ways.
In the early 1920s Frederick Banting and Charles Best discovered insulin under the directorship of John Macleod at the University of Toronto. With the help of James Collip, insulin was purified, making it available for the successful treatment of diabetes.
Percy Julian, Russell Marker, and Carl Djerassi were among the many scientists in the first half of the 20th century who participated actively in the synthesis and large-scale production of steroids—both cortisone and the sex hormones—from plant compounds.
Daniel Bovet was awarded the Nobel Prize in physiology or medicine in 1957 for his work on synthesizing compounds that inhibit the action of certain body substances, especially substances that act on the vascular system and muscles, such as adrenaline, histamine, and acetylcholine.
These French scientists each contributed to the development of chlorpromazine (Thorazine), a pioneer drug for treating mental illness introduced in the 1950s. It was one of the earliest antipsychotics, which work by interacting with and regulating brain chemistry.
George Hitchings and Gertrude Elion were pioneers of rational drug design. During their long collaboration, they produced a number of effective drugs to treat a variety of illnesses, including leukemia, gout, malaria, and herpes.
Using the principles of rational drug design and the concept of physiological receptors, Black discovered a new class of cardiovascular drugs, the beta-blockers, and a class of antiulcer medicines, the histamine-2 (H2)-blockers.
In the 1970s Miguel Ondetti and his colleagues at E. R. Squibb used the principles of rational drug design to develop a new means of treating high blood pressure, or hypertension. The new drugs were called angiotensin-converting enzyme (ACE) inhibitors.
Alfred Alberts, Arthur Patchett, and Georg Albers-Schönberg, scientists at Merck in the 1970s, discovered lovastatin, the first drug to fight “bad” cholesterol by intervening with the body’s own cholesterol synthesis.
Since its introduction in 1988, Prozac has been hailed as a wonder drug, a safe antidepressant that is more effective than those of previous eras. The development of this groundbreaking drug was undertaken by three researchers: Ray Fuller, David Wong, and Bryan Molloy.