What do a scientific prize, an explosive compound, and heart disease have in common?
It is hard to avoid Alfred Nobel in Stockholm.
There are streets, a park, and a museum named after him. One of his former factories is now a café and conference center. In October each year, Nobel dominates the headlines when winners of the prize bearing his name are announced. And during Nobel Week in December, laureates come to Stockholm to receive their award from King Carl XVI Gustaf of Sweden. The awards ceremony and banquet are a glamourous, royal affair. The attire for these events is formal and, just like the Academy Awards, evening gowns can be used to make a statement. My favorite is that of Dr. May-Britt Moser; her dress was adorned with beads formed into the neurons she studies (and for which she was awarded a Nobel Prize).
But I digress. I actually wanted to write about nitroglycerine.
Nobel made history and his fortune when he created dynamite by combining nitroglycerine and diatomaceous earth (basically fossilized diatoms, a type of algae that makes a “shell” out of silica). He patented dynamite in 1867 as a safer alternative to nitroglycerin, which was notoriously unstable.
Nitroglycerine interests me for a few reasons. Based on its name, you can assume that it contains my favorite element, nitrogen! Its chemical formula is C3H5N3O9.
It is explosive. But it also is used as heart medicine.
The explosive medicine. How cool is that?
In medicine, nitroglycerine is used as a vasodilating agent to treat angina pectoris.
In plain language, angina pectoris is chest pain or discomfort that results from the heart not getting enough blood and oxygen. Angina is a symptom of coronary heart disease. The term derives from the Latin angere (to strangle) and pectus (chest) and can be translated as "a strangling feeling in the chest". Vasodilate means to widen blood vessels.
In short, nitroglycerine relives symptoms of angina by widening blood vessels to the heart. It does not address the underlying heard disease.
The Italian chemist Ascanio Sobrero (1812-1888) is credited with discovering nitroglycerine in 1847. Previously, scientists had noticed that materials like starch and cotton could become explosive when treated with nitric acid. Sobrero experimented with dissolving different substances in nitric and sulfuric acids. Nitroglycerine was the product of a mixture of these acids and glycerin. At the time, glycerin was a natural by-product of the soap-making process. Today it is widely used in foods as a sweetener and additive to reduce moisture loss. It is also used in pharmaceuticals and personal care products.
What makes nitroglycerine explosive?
A large amount of energy is stored in the chemical bonds of nitroglycerine. This energy is released in an explosive manner when the bonds are broken, such as by shaking. As one might expect, there was interest in nitroglycerine for military purposes. But because it was so unstable, there were limited uses for it as is. Indeed, Nobel lost his brother and a number of workers in a nitroglycerine-related accident. This led to him to experiment with different additives to make it safe to handle for use in blasting rocks for tunnels, construction, mining, etc.
How did an explosive come to be used as a human drug?
Early on, Sobrero realized that nitroglycerine had strong effects on the human body. He found that tasting small quantities of the substance caused extreme headaches. I am not sure sure why he would taste something that he made in the laboratory (and that he knew to be highly explosive); but hey, curiosity makes you do things you might question later. Sobrero and others conduct experiments on themselves and other human volunteers, testing the effects of different amounts of nitroglycerine.
Interestingly, one of the experimenters, Constantin Hering, thought that nitroglycerine had the potential to cure headaches. This seems rather crazy today, but at the time some believed that “fighting fire with fire” could lead to cures. So one could treat a headache by causing one. Needless to say, that use of nitroglycerine did not catch on.
Nitroglycerin Aktiebolaget; Tekniska museet arkiv
Meanwhile at Nobel’s dynamite factory in Vinterviken, outside Stockholm and pictured above, there were interesting developments. Some workers complained of headaches while they worked but which disappeared during the weekend. Other workers who had previously experienced chest pain during the weekend felt relief while at work.
Ultimately, the work of Lauder Brunton and William Murrell led to the clinical use of nitroglycerine, as described in Murrell’s 1879 paper: "Nitroglycerin as a Remedy for Angina Pectoris." To this day, nitroglycerine is used to prevent and treat angina.
It would be more than 100 years until we understood how nitroglycerine works on the body. To bring the story full circle, Robert Furchgott, Louis Ignarro, and Ferid Murad were awarded a Nobel Prize in 1998 “for their discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system".