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Jun. 3, 2016 Impact Chemistry

Chemists at the front of RIKEN elixir of health and wealth

The pioneering research of two RIKEN chemists in the early twentieth century had a major impact on the organization’s success

Image of a bottle of RIKEN Vitamin Profits from selling bottles of RIKEN Vitamin sustained half of RIKEN's entire research budget during the years between World War One and World War Two. © 2016 RIKEN

Until Umetaro Suzuki isolated the first vitamin in 1911, no one had seen one of these miracle molecules that could prevent vitamin-deficiency diseases such as rickets, scurvy and beriberi.

Suzuki was born in Shizuoka in 1874. He studied agricultural chemistry at a prestigious university in Tokyo. Like many of his Japanese contemporaries in the natural sciences, he then moved to Europe to continue his postdoctoral research. In Germany, he worked under the Nobel-winning chemist, Emil Fischer, who urged him to focus on research pertinent to Japan, warning that competing with Western scientists would be a losing game.

Suzuki took Fischer’s advice and returned home in 1906, thinking about rice. He had heard of beriberi, a life-threatening nerve disease characterized by wobbly knees and paralysis. Many sailors in the Imperial Japanese Navy who lived on a diet of white rice had developed the affliction. In the late 19th century, Christiaan Eijkman, a Dutch physician living in Java, discovered that chicks fed brown rice instead of milled and polished rice did not develop beriberi. Suzuki wondered what was hidden in the bran. While working as a researcher at the University of Tokyo, he found out that the vital nutrient was thiamin, or vitamin B1, which he named aberic acid.

Several years after Suzuki’s discovery of the first vitamin, he joined the newly established Institute of Physical and Chemical Research, now known as RIKEN. In 1918, a sharp increase in the price of rice caused riots throughout Japan. Suzuki was concerned that the country’s staple food was being wasted on sake, and was determined to produce a synthetic version of the traditional liquor. He mixed succinic acid, lactic acid, some amino acids and sugars in a watered-down ethanol solution to create the same flavor and effects of fermented rice wine.

Masatoshi Okochi, an enterprising president of RIKEN, supported the large-scale production of RIKEN-shu, which was sold under the name RIKYU—a brand still stocked in liquor stores today, under new owners and with refined ingredients.

Ample vitamins

It did not take much time before Suzuki hit on an even bigger commercial blockbuster, through the diligence of Katsumi Takahashi, a student who joined Suzuki’s laboratory at RIKEN after graduating from the University of Tokyo. By then, researchers in the United States had discovered another vitamin, known as vitamin A, in animal fats, and doctors were using it to treat the contagious and deadly disease, tuberculosis. Difficulty in extracting the vitamin meant production could not keep up with global demand. Suzuki, who had become director of RIKEN’s chemistry division, set Takahashi the task of purifying and clarifying the chemical structure of vitamin A. This would enable its production on a large scale.

It didn’t take long for Takahashi, well trained in handling lipids, to purify vitamin A from cod liver oil in 1922. He transformed the oil into soap, treated the unsaponified portion with a series of chemicals and distilled it. 20 kilograms of cod liver oil yielded approximately 10 grams of transparent, viscous ‘biosterin’, or pure vitamin A. The substance was bitter but odorless, and had a yellowish-red tinge.

“With an ample amount of the substance thus obtained, the authors have been able to make a thorough study on its physical and chemical properties, and its physiological effects,” describes a paper Takahashi published in 1925, the same year he died of typhus when only 32. The paper went on to present the first evidence of the toxic and potentially lethal effects of a vitamin overdose. It was a prescient finding considering the prevalence of vitamin deficiencies around the world at the time.

Windfall profits

List of various vitamins After discovering the first vitamin, B1, Umetaro Suzuki continued his research into many more vitamins, including vitamins A, B6, C, D and E. © 2016 RIKEN

Takahashi’s vitamin A research was a financial windfall for RIKEN. Its success was driven by President Okochi’s revolutionary strategy to commercialize inventions to generate revenue—he called it ‘science-driven industry’. “Looking back, it may well be called the frontrunner of innovation today,” says Tomoya Ogawa, science adviser to RIKEN, who considers himself an “academic grandchild of Suzuki”.

Okochi invested in a venture called Rikagaku Kogyo in 1927, which sold vitamin A in copper-colored glass bottles under the brand name RIKEN Vitamin. During the interwar period, sales of RIKEN Vitamin raised profits worth JPY 600,000 a year, enough to cover half of RIKEN’s entire research budget. Almost 70 ventures were born during Okochi’s presidency.

In 1949, the vitamin business spun off from RIKEN, with the establishment of an independent company named RIKEN Vitamin Oil, known today as RIKEN Vitamin. The company took advantage of molecular distillation techniques developed by nuclear physicists at RIKEN to scale up industrial production. In 1958 alone, it produced 120 trillion international units (IU) of vitamin A, fulfilling 60 per cent of global consumption—the recommended daily intake for a healthy adult ranges from 2,000 to 3,000 IU.

By the 1950s Japan’s booming vitamin industry was facing stiff competition from abroad, as chemists from the European pharmaceutical giant, Hoffmann-La Roche, discovered how to manufacture synthetic vitamins. Artificial vitamins are easier to mass-produce than those extracted from natural sources.

Suzuki continued his research into vitamins, including vitamins B6, C, D and E, until his death in 1943. That year, he was awarded the Culture Order and the First Class Order of the Sacred Treasure. To this day, researchers like Ogawa remember him as a scientist who “pursued strategic basic research mainly from the viewpoint of nutrition and good health for the Japanese people”.

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