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The History of Enzyme Supplements

Category: Educational Articles

Dr. Jokochi Takamine

The use of enzymes for dietary supplements began with a young Japanese immigrant, Jokochi Takamine.

Born in Takaoka, present-day Toyama Prefecture, in November 1854, Takamine spent his childhood in Kanazawa, capital of present-day Ishikawa Prefecture in central Honshu. Considering his background, it is no surprise that he became an inventor in the world of koji: His father was a doctor; his mother a member of a family of sake brewers.

From an early age, Jokochi showed an aptitude for languages and science and he was encouraged by his father to pursue western scientific interests. At the age of 12 he began the study of “foreign science” in Nagasaki; at 16 he was admitted to the medical school in Osaka; at 18 he transferred to a program in chemistry at the College of Science and Engineering in Tokyo; at 24 he was selected by the government to study technology at the University in Glasgow. While in Scotland he perfected his English, studied the industrial revolution and specialized in the practice of fertilizer manufacturing. Then he returned home to Japan and took a job with the newly established Japanese Department of Agriculture and Commerce. The goal was to apply western technology to Japanese products.

However, his stay in Japan was short. In 1884, he was sent to the USA to be a co-commissioner of the Cotton Exposition held in New Orleans, Louisiana. While in New Orleans, he continued his research into fertilizer powders, and more significantly, fell in love with his landlord’s daughter, Caroline Field Hitch. Before returning to Japan at the end of the Cotton Exposition, Takamine proposed marriage to Caroline, promising to return as soon as he had established himself financially. Good to his word, after having been appointed Acting Chief of the newly organized Japanese Bureau of Patents and Trade Marks, he was back to the USA within two years. The wedding took place New Orleans in 1887. It was an unconventional match for the era and one which would eventually cement Takamine’s connection to the USA.

On their honeymoon, the young couple went to South Carolina where they visited fertilizer manufacturing plants and then to Washington D.C. where Takamine studied U.S. patent law. Finally they traveled west to California and then sailed to Japan. Once in his homeland, Takamine established the first Japanese super-phosphate plant to supply fertilizer to the rice farmers, called the Tokyo Artificial Fertilizer Company. The young couple lived near the fertilizer factory. Two sons, Jokichi Jr. and Eben were born in quick succession in 1888 and 1890. Although both children were healthy and the young couple was undoubtedly in love, the situation was difficult. The neighborhood around the fertilizer plant was “neither comfortable nor respectable” and it smelled bad. Caroline’s blond hair and blue eyes made her conspicuous. Jokichi’s mother made it clear that she did not like her foreign daughter in law. Because Caroline was unhappy living in Japan, Jokichi sought new business opportunities in the USA. He knew he could not compete in the well established American fertilizer industry. Therefore in a stroke of genius, Takamine decided to reverse what was then the usual cultural flow of technology. Rather than adopting a western technology to a Japanese enterprise, Takamine adapted a Japanese technology to a western industry.
Believing that a diastatic enzyme obtained from koji, Aspergillus oryzae, could revolutionize the American distillery industry, Takamine and his young family returned to the USA in 1890. He worked first from Chicago and then from Peoria, Illinois, adapting the koji process for the beer and whiskey business. Sponsored by the Whiskey Trust, the Peoria distillery where he was employed was successful because the fungal diastase was faster to saccharrify starch and cheaper to produce than the diastase from malt.

Unfortunately but perhaps predictably, the local malt manufacturers did not welcome Takamine’s innovation. Historical records are unclear, but there is evidence of racist labor agitation and perhaps even arson. The distillery where Takamine worked was burned to the ground and he was financially ruined. To make matters worse, he was stricken with an acute liver disease and had to have emergency surgery in Chicago. It was the low point of his life, and Caroline sold arts and crafts to support the family. Fortunately, Takamine recovered his health as well as his optimism. In 1894 Takamine applied for and was granted a patent entitled “Process of making diastatic enzyme” (U.S. Patent No. 525,823) on his method of growing mold on bran and using aqueous alcohol to extract amylase. It was the first patent on a microbial enzyme in the USA. Further, Takamine recognized that the diastatic properties of the Aspergillus enzyme had potential medical applications. He licensed his enzyme preparation to the Parke-Davis company of Detroit, Michigan, under the brand name “Taka-diastase.” Parke-Davis aggressively marketed it as a digestive aid for the treatment of dyspepsia said to be due to the incomplete digestion of starch. This is the first recorded account of enzymes being used for oral consumption as a medicinal in the world. Takadiastase was enormously successful and Takamine became a consultant to the company. With Parke-Davis as his patron, he moved his family to New York and established an independent laboratory on East 103rd Street in Manhattan.

Once established in New York, Takamine turned his attentions to another biological product that is active in minute amounts, namely the “internal secretions” associated with glands, in particular a blood pressure raising principle from the adrenal glands. Through his research, he invented a method of crystallizing the adrenal-gland hormone, which he patented in 1900 entitled “Glandular extractive product” on a blood pressure raising principle. He named the crystalline substance “Adrenalin” and presented two papers, one before the Society of Chemical Industry and the other before the New York State Medical Society. In 1901, he published two single author papers in the scientific literature and applied for and was awarded the right to the word “Adrenalin” as a USA trademark. Almost immediately, Parke-Davis started manufacturing the product and selling it under the trade name of Adrenalin. Adrenalin was the first of many ‘blockbuster’ drugs introduced during the 20th century.

Takamine became a millionaire in a relatively short time and by the early 20th century was estimated to be worth $30 million. The emperor of Japan acknowledged Takamine’s success by conferring the Order of the Rising Sun, Fourth Class. The emperor also sent fifteen imperial cherry trees to Parke-Davis where they were planted in front of the administrative offices.

takamine-smallTakamine used the new royalties from Adrenalin and the continuing royalties from Taka-Diastase to expand his business operations in both enzyme and pharmaceuticals. He founded three major companies; Sankyo Pharmaceutical Company of Tokyo, the International Takamine Ferment Company of New York, and the Takamine Laboratory of Clifton, New Jersey.

In addition to managing his own companies and his investments, he turned his energies towards improving the position of the Japanese in the USA. It was an era when many Asian immigrants were denied basic civil rights and there was widespread discrimination against Japanese. Nevertheless, his wealth allowed him to move in high society where he made a point of dressing in Japanese clothes and talking about Japanese culture. His homes were built in the Japanese style, and furnished with traditional Japanese furniture so that Americans could be exposed to the refined aesthetic of his native country. When he learned that the US President’s wife, Mrs. William Howard Taft, was working to beautify the Tidal Basin Area around the Potomac River in Washington, D.C, Takamine put up the money to have 3,000 cherry trees sent to Washington, D.C., where they remain to this day a symbol of beauty and friendship between Japan and the U.S.

Jokochi Takamine died in 1922 of the liver ailment that had plagued him most of his life. Jokichi, Jr. died under mysterious circumstances well before World War II, and with his death the International Ferment Company of New York was dissolved. Takamine’s other son, Eben, continued running Takamine Laboratory. After his death in 1953, Eben’s widow sold it to Miles Laboratories of Elkhart, Indiana, which continued the manufacturing and selling of diastase. Miles was later acquired by Bayer Corporation, who then sold the business to Solvay, a Belgian company. Solvay in turn sold the business to Genencor International in 1996.

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