Before the war, Germany was the leading producer of industrial chemicals, including textile dyes and solvents, as well as drugs. Yet due to the British blockade, which began shortly after the war, Germany could no longer import food or raw materials for its chemical industry, and other nations no longer had access to German chemicals. These raw material shortages led scientists from both sides of the conflict to search for alternatives to manufacture important materials, and led to cells being used to manufacture nonfood products for the first time.
Due to the blockade, Germany no longer had access to glycerol, an important component to manufacture the explosive nitroglycerine. To get around this shortage, Wilhelm Connstein and Karl Ludecke, together with Carl Alexander Neuberg and Elsa Reinfurth, used yeast to manufacture glycerol. They showed that adding sodium sulfite to a fermentation prevented the reduction of the acetaldehyde, an important metabolic intermediate, in the production of ethanol. Inhibiting the metabolism in this way meant that the fermentation would produce large amounts of glycerol instead. Germany’s United Chemical Works patented the process in 1915, and immediately adopted it for the large-scale production of glycerol. This allowed Germany to produce more than 1,000 tons of glycerol per month.
Great Britain was also interested in alternative methods to manufacture important chemicals during the war. As with Germany, developments in the cell culture processes provided a way to meet this increased demand. But the work actually began before the war. In the early 1900s, rubber was widely used in everything, from the auto industry to pipe stems. At the time, it was isolated from natural sources, and Brazil had a virtual monopoly on the production. A shortage of rubber from 1907 to 1910 highlighted the need for synthetic alternatives.
In 1904 Dr. Chaim Weizmann came to the UK and became a researcher at the University of Manchester. His research focused on the use of fermentation to produce butanol, a precursor to synthetic rubber. Weizmann and his colleagues, in collaboration with the Pasteur Institute in France, initially identified a bacterium that could produce butanol and amyl alcohol. Yet the potential commercial impact led to conflicts amongst the team, and Weizmann began his own research.
In 1912, Weizmann isolated the bacterium, Clostridium acetobutylicum, which could ferment grain to produce butanol. The bacterium also produced acetone. Acetone was an essential solvent in the manufacture of the explosive cordite. Prior to World War I, acetone was manufactured from wood. However, in 1914 it became obvious that to support the war effort Britain would face a shortage of acetone, with an annual requirement greater than five times the production of the entire American wood industry in 1914. After other attempts to produce acetone from fermentation failed, the British admiralty turn to Weizmann. Using his process, the production of acetone increased fourfold to more than 1,000 tons per week.
Beyond its usefulness, Weizmann’s process was also unique. Traditional fermentations were carried out in oak casks under non-sterile conditions. Weizmann’s process required aseptic conditions. It used aluminum vessels, steam to sterilize the vessels, and heat to sterilize the raw materials. This was the first commercial-scale process that utilized such a sophisticated approach.
These two historical anecdotes illustrate important concepts in the use of cells for manufacturing. First, cell culture could be used to produce chemicals, not just food and drink. This was an important development in the use of cell culture and fermentation for industrial manufacturing. Second, aseptic processing conditions gave more control over the cell culture and what the culture produced. Modern biomanufacturing expends significant effort in ensuring that cell cultures or fermentations are aseptic.
