Some people are more famous than they ought to be, and some less. Jokichi Takamine falls squarely into the latter category. He was a scientific bridge linking Japan, the United Kingdom and the United States. He produced the first effective asthma medicine, the first effective indigestion remedy and revolutionized the production of beer and whisky by introducing Japanese knowledge to western alcoholism, and yet his English Wikipedia entry is shorter than that of Chesney Hawkes. Let this introduction be the feeblest of efforts to put that oversight right.
Jokichi Takamine was born in Takaoka, Toyama, Japan, in 1854, and the citizens of that fair city still take every opportunity to remind visitors of the great man who hails from their town. He moved to Kanazawa while still a baby (a fact generally unacknowledged by any of the materials produced in Takaoka), where his physician father noticed the young boy`s aptitude for both languages and science and encouraged him to follow his interests, even if it meant leaving home. So it was that at the tender age of 12, he won a scholarship to study Western science and moved almost 1000 miles west to Nagasaki (a fact which, in turn, is absent from any mention of Takamine in the Kanazawa records. Nagasaki, however, had such an embarrassment of notables at this time that the young Takamine is scarcely acknowledged by the city in any case, so perhaps it is as well for Kanazawa to claim him as their own).
Nagasaki at that time must have been one of the most interesting places in the world for a young boy to live. The rest of Japan was struggling to cope with the influx of foreign culture that followed the forced opening of the country by Commodore Perry in 1853, but Nagasaki, ever an anomaly, was largely continuing with business as usual. While Japan was sealed off to foreigners for the past two centuries, Nagasaki had been allowed to trade much more freely; with the Dutch who were permitted to trade from the island of Dejima in Nagasaki harbour, with the Portuguese, who were more or less tolerated as long as they didn`t attempt to continue the proselytizing work of their Jesuit predecessors, and the Chinese, who sailed in and out of Nagasaki, buying and selling anything which would fetch profit such as silks, art, porcelain and even firearms. Add to this the Indonesian slaves of Dutch traders, the trade with Korea which had continued through war, famine and pestilence for well over a thousand years, and occasional Russian trading envoys, and the freedom given to all these people by the opening of the country ten years before Takamine`s arrival, and we can perhaps get a sense of the wild wonder which would have seized him upon his arrival in this international city. Even today, the first time visitor to Nagasaki can sometimes find himself lost in a reverie, and fancy that he spies a busy Chinese merchant rushing off to the house of a noble to sell his latest batch of highly fashionable Yangshao silks.
Takamine was sent to live with a Dutch family, with whom he continued his study of English, and attended a school run jointly by the Portuguese consulate and local government. Here he was first introduced to Western science and medicine, and excelled at the school. This led him to be recommended to medical school in Osaka at the unusually young age of 16. Osaka is considered in Japan to be a city of merchants, as opposed to the stiff formality of Tokyo, a city of samurai. While little evidence remains of Takamine`s stint in Osaka, it is easy to imagine that some of the commercial spirit rubbed off on the young boy, paving the way for the great success he enjoyed in the United States.
After two years in Osaka, he moved on to the stiff formality of Tokyo. Having decided that he would make a better chemist than physician, he entered the chemistry course of the Tokyo College of Science and Engineering, which would later become Tokyo University. Tokyo was perhaps not as comfortable as Nagasaki with the opening of Japan in this era, but the national government was fully aware that without Western knowledge, the country would have no chance of becoming a developed nation that could resist the imperial tide overrunning other parts of East Asia. Hundreds of foreign advisers thronged every department of government, building railways, teaching at the imperial universities, designing ports and even organizing western style balls and dances at the Rokumeikan, the cultural centre where many Japanese were introduced to Western manners for the first time.
More importantly for Takamine, the government was also sending great numbers of Japanese abroad to study the gamut of disciplines, be it science, governance, law, education, economics or any of a hundred other areas in which Japan badly needed expertise in order to build a modern state. In 1871 the Iwakura mission was sent out, modeled on the great missions of Peter the Great when he was in the process of Westernising Russia in the 18th century (though one presumes that the Iwakura mission wasn`t such a boozy affair as Peter`s famously hedonistic Embassies). The Iwakura mission visited Glasgow in 1872, and while there they formed relations with the University of Glasgow. As a result, the Japanese government was able in the coming years to send out students to the university. With his fluent English and exemplary academic record (he graduated at the top of his class in 1879), Takamine was chosen to receive a three year scholarship to further his study of chemistry in Glasgow, and set out for Scotland in 1879, arriving in early 1880.
Scotland seems to have treated the young Takamine well, for he thrived there, not only studying at the university but also embarking on a personal study of the industrial revolution. He put this to practical use by specializing in the manufacture of fertilizer, another area which the Japanese government had marked out as vital to the modernization of Japanese agriculture. He also developed the knowledge of enzymes which would later allow him to revolutionise alcohol production. Around half a century later another aspiring Japanese chemist, Masataka Taketsuru, would study at Glasgow and, after working in whisky distilleries across the Mull of Kintyre, introduce whisky to Japan and found the first domestic distillery. I am powerless to suggest what odd karmic forces link Japanese chemists so closely with both Glasgow University and alcohol production, but it is surely a link which has brought great benefits to all parties involved.
After three years in Glasgow, Takamine headed for home. He started work immediately for the Japanese government at the Ministry of Agriculture and Commerce where he was tasked with introducing Western learning to Japanese farming, but his stay was to be a short one. He was sent in 1884 to be a co-commissioner representing Japan at the Cotton Exposition in New Orleans. It is easy to imagine that without this trip he may have stayed in Japan for the rest of his life as an exceedingly competent but otherwise undistinguished government bureaucrat, making small changes to Japanese agriculture and generally working for the good of the nation. In New Orleans, however, he lived in the house of a retired military man, Colonel Ebenezer Hitch. Takamine fell in love with his daughter, Caroline Field Hitch, and this kept him linked to the USA for the rest of his life. He also met Lafcadio Hearn, one of the earliest and most successful writers about Japan, who later partly credited Takamine with stoking his interest in the country and persuading him to travel there in 1890. In what must have been a necessarily whirlwind romance, before the end of the Exposition Takamine had proposed marriage to Caroline, and promised to return to America once he had made himself financially secure to follow through on the proposal. The match was an unconventional one for the period, but the couple were evidently deeply committed to each other, and after two years working in Tokyo at the Japanese Bureau of Patents and Trademarks Takamine returned to America. The happy couple were married in the height of a New Orleans summer, on August 10th 1887.
The couple went on honeymoon to South Carolina, where in addition to the usual sightseeing trips they visited fertilizer factories (it is unrecorded whether Caroline had any second thoughts about the marriage at this point, but you might sympathise with her if she had). Indeed, it seems to have been more of a working holiday than a honeymoon, for as well as the aforementioned fertilizer production study, Takamine also researched American alcohol population and went to Washington DC to take an intensive course in American patent law. What a hopeless old romantic!
Given his study of patent law, we might speculate that he was already laying the foundations for his future business ventures in the USA. Before that, however, he would return once more to Japan with his wife, a venture that would be financially rewarding but personally difficult for him. On his return, he again worked on applying Western technology in Japan, but this time to a private rather than governmental enterprise. He set up the first super-phosphate factory in Japan with Baron Shibusawa Eiichi and Masuda Takashi, introducing and selling chemical fertilizer to Japanese rice farmers for the first time; up until then night soil had been the major source of fertilizer for rice, with the `soil` of the rich even fetching higher prices than that of the poor because of their better diet! You know a class divide is really entrenched when even the price of excrement is affected.
The venture did not go well at first, but after Takamine set up a new sales structure, making contacts with influential fertilizer merchants and allowing them monopoly rights over wide areas the business really took off, and the Tokyo Artificial Fertilizer Company soon established chemical fertilizer as the norm in rice cultivation. Jokichi and Caroline were also blessed with two children, Jokichi and Eben, born in 1888 and 1890 respectively. However, everyday life was tough. The couple lived in the insalubrious and perhaps rather malodorous district around the fertilizer plant, and the couple lived with Takamine`s mother, Yukiko. I don`t want to overplay the `evil mother-in-law` card, but Caroline later recalled that not only did Yukiko not approve of her, she refused to acknowledge her existence at all, which must have made for slightly awkward family dinners. Caroline grew understandably unhappy at this state of affairs, and Takamine was soon persuaded that he should continue pursuing his business interests in the United States.
Takamine knew he would not be able to compete in the old and well established chemical fertilizer industry in the United States. Thus, rather than applying Western technology to Japanese industry, he pondered how he could apply Japanese technology to Western industry. Admirably, he decided on alcohol production as one area where this could profitably be attempted.
The science of alcohol production
Alcohol is produced when yeast acts on sugar to produce alcohol and carbon dioxide, as I`m sure we all remember from high school science class. The majority of foodstuffs from which alcohol is made do not necessarily contain large amounts of sugar; potatoes for vodka, barley for beer and whiskey or rice for sake are not what any of us would consider a sweet treat. The starch in these foods must be broken down into sugars before alcohol production can begin, and this is done by a group of enzymes known as amylases (also known as diastases). In the West, amylases for brewing were traditionally obtained from malted barley. In Japan, however, a rice mould known as koji is normally used for the same purpose. It is likely that Jokichi would have been familiar with koji from the sake distillery that belonged to his mother`s family, and from his time in Glasgow he would have been familiar with amylase derived from malted barley. He would therefore have known that while the two are similar, the enzyme derived from koji is more active and thus more effective. In fact, koji is considered so important in Japan that the mould from which it comes, Aspergillus oryzae, is a designated national fungus. Whether any other country has seen fit to designate a national fungus is, I`m afraid, not something I was willing to give any time to research fully, but I find it unlikely.
Coming to America
Takamine took this knowledge to the United States in the 1890 and tried to sell it to the whisky industry. He was soon employed by the Whiskey Trust (and who wouldn`t want to go to one of their Christmas parties?), who put him in charge of whisky production at the Peoria distillery. He experimented further with enzymes derived from wheat bran while working here, and ended up turning round the fortunes of the distillery, which now had access to a cheaper, more effective enzyme to break down starch. He founded the Takamine Ferment Company in 1891 to market the enzyme, and it seemed like the family had got off to a flying start in the States.
However, the local malt manufacturers certainly did not welcome this new foreign intruder on their business with his irritatingly effective foreign methods. American citizenship laws at the time prevented the naturalization of Asians nationwide, and in some areas state-level laws entrenched discrimination further. Fear of financial ruin because of Takamine`s innovations and endemic xenophobia meant that Takamine was targeted by competitors. His workers were encouraged or threatened to strike, and his family were excluded from local businesses. This came to a head when the Peoria distillery where he made his living was destroyed in a fire. It was never proved to be arson, but in the circumstances it must be considered a possibility. Takamine was financially ruined, and at the same time he was struck down with liver disease which required emergency surgery in Chicago, stretching the family budget even further, and Caroline took to selling arts and crafts to support the family; something of a step down for the daughter of a famous Southern dynasty.
In hospital, with no money and an uncertain future, you might forgive Takamine for wanting to give up, to flee back to Japan and return to the safety of a Japanese government job and a solid pension. He was made of sterner stuff, though, and it was while in hospital that he struck upon his next idea, the one that would make him rich and secure his future. He was considering other uses for the wheat bran enzyme he had developed, and to this end applied for a patent for the method in 1894, and was granted U.S. Patent No. 525,823 for deriving amylase from wheat bran using aqueous alcohol. This was the first patent on a microbial enzyme taken out in the United States.
Takamine would have known from his medical training, and perhaps been reminded by his time in hospital, that indigestion was at this time thought to be caused by the incomplete digestion of starch in the stomach. He thus struck upon the idea that his enzyme preparation could be used to break down starch in the stomach just as it was used to break down starch in barley. He marketed it through the drugmakers Parke, Davis and Company, and the resulting medicine, Takadiastase, became the world`s first commercial indigestion recipe. It was so successful that you can still pick it up in any pharmacy in Japan or the United States today. Perhaps ironically, this Japanese product was sold throughout the war when all other Japanese products were banned in the United States, and had American citizens known the truth about its origins it may have done more harm than good for their dyspepsia. It also took off immediately in Japan; the great novelist Natsume Soseki grudgingly took it daily, as does the human hero of his 1905 novel I am a Cat. Takamine became an adviser to Parke-Davis, and through his patent earned enough money not just to be secure, but to be fabulously wealthy; by 1900 he was a millionaire, and he moved to New York with his family and set up a private laboratory in Manhattan.
Takamine now had the financial freedom to devote himself to scientific research, and he applied himself to the problem of obtaining adrenaline. Polish chemist Napoleon Cybulski managed to extract the substance in impure form in 1895, and in the same year George Oliver and Edward Schafer showed that it could be used to raise the blood pressure of laboratory animals, but the impurities in the extracts obtained often caused the treatment to be more dangerous than the diseases it was meant to cure. Professor John Abel of Johns Hopkins University had also researched the problem, so Takamine visited him many times in the summer of 1899 to ask him about his methods. He employed an assistant, Keizo Uenaka, and between them they developed a method of deriving pure adrenaline in crystalline form from the adrenal glands of sheep and oxen. At a stroke, they had obtained a drug which could be used to treat, among other things, asthma (the first effective remedy for the condition), anaphylactic shock, cardiac arrest, and croup. It was a public and medical sensation; champion boxer Gene Tunney never entered the ring without a vial of the liquid to hand, and it was also used to prevent haemhorraging during surgery, one of the most important developments since anaesthetic. Takamine applied for the patent which was granted in November 1900, making him the first man to hold a patent on a purified hormone. The following year he presented and wrote single author papers to the New York Medical Society and the Society of Chemical Engineering, and was awarded the right to use the word Adrenalin as a trademark.
John Abel, by now perhaps wishing that he too had studied patent law while on his honeymoon, felt that he had been cheated by Takamine, and also claimed that the chemical research was flawed. Takamine countered this by breaking down his original single patent application into five, to guard each and every step of the process against unlicensed imitation. He was further challenged by H.L. Mulford, a rival of Parke-Davis, who took the company to court arguing that Abel was the progenitor of the discovery, and that as a natural animal extract the hormone could not be patented. The details of the case are too complicated to go into here, but Judge Learned Hand (and if anyone knows a better name for a judge I should like to hear it), having spent many days studying the technical details, delivered a summary that concluded with the following words, which would change the relationship between law and science permanently;
“I cannot stop without calling attention to the extraordinary condition of the law which makes it possible for a man without a knowledge of even the rudiments of chemistry to pass upon such questions as these”.
Judge Learned Hand ruled in favour of Takamine, and his discovery and patents were safe.
Reaping the rewards
Takamine used the great wealth which resulted to expand his business activities. He founded three more companies; Sankyo Pharmaceutical in Tokyo (now the Daiichi Sankyo Pharmaceutical Company, the largest drugmaker in Japan), the Takamine Laboratory of New Jersey, and the Takamine Ferment Company. He also turned his attention to improving the lot of Japanese in the United States, and to improving Japanese-American relations. He founded the Japanese Society of New York and the Nippon Club, and he often appeared at both in traditional Japanese dress to talk about Japan and its culture. He also frequently entertained the cream of New York society at his Japanese style home, Shofuden, and brokered and financed the gift of 2000 cherry trees from the Mayor of Tokyo to Washington City in 1909 when he learned that the First Lady, Helen Taft, was working to beautify the Potomac River basin. He was recognized by the Emperor of Japan in 1915, who awarded him the Fourth Order of the Rising Sun. He continued to work to bridge the gap between the two countries, and even as his health began to fail him in the 1920s he still insisted on attending the Washington Naval Conference as part of the Japanese delegation; that he was attending international political conferences shows how highly he was regarded in both Japan and the United States at this time.
The end of the road
Takamine had pushed himself too hard at the conference against the advice of his doctors and he took to his bed in December 1921 with a severe recurrence of the liver ailment that had previously plagued him in Chicago. He was not to recover this time, and after fighting the disease for over half a year he passed away peacefully in July 1922. He was buried in the Woodlawn Cemetery in New York, where his mausoleum contains a stained glass window depicting Mount Fuji; his attempt to bridge the gap between Japan and America continuing in death as it had in life.
Takamine`s genius for me lay in being as skilful an entrepreneur as he was a chemist. He was a pioneer in biotechnology and endocrinology, and also an extremely shrewd businessman. Perhaps the best summation of his achievements was that given by his long-time friend, J.L.C Clarke on the occasion of Takamine`s funeral.
“Apart from his devotion to science, it was his dearest wish to promote abiding and enduring friendship between the land of his birth and that of his adoption. In the field of the chemistry of life he had created powerful corporations to develop and apply his valuable inventions and discoveries, always keeping before him big cherished ideal of a union between Japan and the United States based on a common economic interest and mutual esteem. In his pursuit of this ideal he incessantly worked with tireless zeal and grim determination, giving most unstintedly, and was rightly spoken of as an uncrowned Ambassador of Good-Will between the two nations, An intense lover of Japan, its ancient art, its domestic virtues, its rich traditions, he became an equally ardent lover of the United States, its high ideals, its balanced freedom.”
From a humble rice mould came one of the most remarkable lives of modern Japan. Jokichi Takamine gave the world the technology which allows for beer and whisky to be produced commercially and reliably, the first effective medicine for indigestion, still available 110 years after first going on sale, and the world`s first effective asthma medicine and remedy for anaphylactic shock. If like me you enjoy a drink, have asthma and sometimes overindulge at dinner, it is hardly going too far to say that few people beyond Thomas Edison have discovered so much which I use and rely on every day of my life. If one man should be more famous than he is, it is surely Jokichi Takamine, who bestrode countries and scientific disciplines to improve American Japanese relations, medical science and the lives of countless millions over the past hundred years. I for one will be raising my next pint of beer, the very beer he helped to produce, to Jokichi Takamine.