MERCK FROM 1668 UNTIL TODAY EXPLORING NEW HORIZONS

Transcription

1 MERCK FROM 1668 UNTIL TODAY EXPLORING NEW HORIZONS

2 02 Cover: Emanuel Merck ( ) Friedrich Jacob Merck s application for pharmacy privileges, 1668

3 03 THE HISTORY OF A COMPANY EXPLORING NEW HORIZONS Page ON PAR WITH THE COMPETITION Page STRIVING FOR PERFECTION Page FOLLOWING THE RULES Page SEEKING MORE KNOWLEDGE Page SHAPING THE TRANSFORMATION Page WORKING TOGETHER Page SHOWING COURAGE Page LIVING RESPONSIBILITY Page TACKLING NEW CHALLENGES TOGETHER Page THINKING STRATEGICALLY Page TODAY UNLOCKING POTENTIAL Page 42

4 EXPLORING NEW HORIZONS I, a native of Schweinfurth, learned the pharmacy trade From Friedrich Jacob Merck s application for pharmacy privileges in 1668 Friedrich Jacob Merck takes a chance. He does not stay in Schweinfurt he wants to go somewhere with his life, to be successful. Following an apprenticeship at a pharmacy in Schweinfurt, the 20-year old leaves his hometown in He goes on to manage the court pharmacy in Danzig as well as to own a pharmacy in Wesselburen, located in Schleswig-Holstein. He finally moves to Darmstadt in the 1660s. Before that, in 1654, court pharmacist Samuel Böckler received permission from Landgrave Georg II to establish Darmstadt s second public pharmacy, which he located next to the castle moat. That pharmacy was now for sale Purchase of the Angel Pharmacy Friedrich Jacob Merck acquires the Angel Pharmacy, which will become the heart of Merck, the oldest pharmaceutical-chemical company in the world. This is the time when pharmacists are using a variety of natural ingredients to produce medicinal compounds according to the formulations described in the pharmacopoeia. However, the formulations are often imprecise, the regulations inconsistent: the manufacture of drugs will long remain an experimental art. Quality and price control are governed by pharmacist regulations and taxes. The Angel Pharmacy is still owned by the Merck family to this day.

5 05 Darmstadt in the mid-17th century

6 On par with the competition And since we wish to maintain high standards in medicine and the liberty of patients with two pharmacies here, we hereby approve Georg Friedrich Merck s request. Landgravine Elisabeth Dorothea von Hesse-Darmstadt, 1682 Friedrich Jacob Merck, who dies childless in 1678, is succeeded by his nephew Georg Friedrich Merck. In 1682, he receives permission from the Landgraviate of Hesse-Darmstadt to continue operating the Angel pharmacy, a competitor to the older Hof-Apotheke Health care reforms lead to changes at the Angel Pharmacy At the turn of the 18th century, major changes are made to drug legislation. Government regulation of medical professions is increased; institutional supply of the population is regulated, standardized and professionalized by social and health policy measures of the Medical Police. The sale of medicines by charlatans, barber surgeons and mongers is highly restricted. This strengthens the position, image and profits of pharmacies, especially in cities with a higher number of wealthy inhabitants provided that the new regulations are applied with a bit entrepreneurial foresight. The young Angel Pharmacy is able to lay the foundations for the future.

7 The Angel Pharmacy of Georg Friedrich Merck At the dawn of the 18th century, the art of pharmacy is still based on traditional texts and knowledge. The materia medica the raw materials needed for medicinal compounds consists of plants, minerals, and human/animal parts. Simple drugs are in use, referred to as simplica. However, diverse complex formulations known as composite are also prepared according to the formulations in the pharmacopeia. But the natural medicinal substances often come from distant regions, making them precious and expensive. Spices such as muscat flowers and cinnamon are among the typical commercial products, as shown in an invoice from The Pharmacopoeia Augustana, published in 1564, will remain the definitive reference work until the beginning of the 18th century.

8 Striving for perfection de arte pharmaceutica bene merentissimus Inscription from the tombstone of Johann Franz Merck, 1741, who had made many great contributions to the pharmaceutical arts Against medical regulations Is Johann Franz Merck guilty? The goods sold and prepared in pharmacies vary widely especially with respect to their efficacy and danger. Often it is the dose alone that transforms a substance from a cure into a poison. In 1720, Johann Franz Merck gives poison to an old and oafish man without independent attestation, contrary to medical regulations, and the man s wife then commits suicide with the substance. Merck is consequently sentenced to pay a fine. In-depth investigations show that the woman was severely ill and highly melancholic. Under these special circumstances, the question concerning guilt is viewed forgivingly, even by the Church, and the punishment abated. Nevertheless this shows once again the very special responsibility that pharmacists bear The Chamomile man The Baroque gravestone of Johann Franz Merck, who made great contributions to the pharmaceutical arts, features a coat of arms with a figure dressed in medieval clothing holding a flowering branch in his hand. In the 19th century, the Chamomile man becomes first the main charge of the family coat of arms and then a symbol for Merck, denoting the origins of the company in the pharmaceutical arts inseparably linked with knowledge of medicinal herbs. Registered as a trademark in 1894, the Chamomile man is used as a picture logo up until the 1950s. In 1935, the Darmstadt sculptor Heinrich Jobst is commissioned to design a bronze figure of the Chamomile man. Not cast until 1954 due to the war, this statue is still located at the Darmstadt site, where the Baroque gravestone of the original Chamomile man can also be found.

9 09 Pharmacy substance vessel

10 Following the rules First and foremost, I will uphold God and His Holy Scripture, not take part in frivolous society and keep away from wanton and frivolous beings; my mind will be devoted solely to God and the worthy art of apothecary Excerpt from Johann Justus Merck s apprenticeship contract, 1744 Human medical care has always been highly regulated. In the mid 18th century, the professional qualifications for pharmacists become even more regulated. Pharmacists have to demonstrate an honorable character, respectable behavior, and social responsibility Johann Justus Merck Pharmacist in our imperial residence Landgrave Ludwig VIII engages Merck as a pharmacist in Darmstadt in Representing the fourth generation of the Merck family in Darmstadt, he assumes management of the Angel Pharmacy. Ten years previously, he had started his apprenticeship at the renowned court pharmacy in Dresden. A certificate dated 1753 indicates further training in Stuttgart. It is certainly not by chance that he chooses this city: the Pharmacopoea Wirtenbergica, first published in 1741 and revised several times in the following years, is considered to be the most modern pharmaceutical formulary of its time. By adhering to the instructions it contains, the pharmaceutical arts can be practiced according to the best available knowledge of the time.

11 An orphaned pharmacy It is not easy to maintain a company over many generations. When Johann Justus and his wife Anna Sophie both die in 1758, their designated heir, son Johann Anton, is not yet two years old. We can only guess how the company is managed during this difficult period. However, one deciding factor is that the grandfather had already ensured that the family be well looked after. Another factor is that the statutory regulations cover such situations: the heritable pharmacy privilege comes under the protection of Landgrave Ludwig and is confirmed, as long as the pharmacy is maintained in a good and integral state. An acting pharmacist takes the pharmacy over and obviously runs it so well that Johann Anton is able to have an exceptionally multi-faceted apprenticeship before he takes over the business. Johann Justus Merck ( ) and Anna Sophie Merck ( )

12 Seeking more knowledge From an early age, Merck dedicated himself particularly to natural history and chemistry and through his research into natural products gained knowledge that went far beyond the commonly known facts Evaluation of Johann Anton Merck when he was hired as a medical assessor, Johann Anton Merck Pharmacy owner and medical assessor In an era that predates independent university colleges and departments, a pharmacist who wants to work scientifically needs a good deal of initiative. Johann Anton Merck does not limit himself to the traditional apprenticeship and time as an assistant before he takes over his father s pharmacy in His goal is the University of Strasbourg, where doctor and pharmacist Jacob Reinbold Spielmann is lecturing on pharmacology and medicine and also offering experiment lectures in his laboratory. Subsequently, Merck travels to Switzerland and Italy and seeks contact with learned scholars. His collection of minerals gives him extensive specialist knowledge. Thus, he gains a reputation for outstanding knowledge through research into natural products, which could enable him to become a professor in this field. This makes him far better educated than the other pharmacists of his era Emanuel Merck takes over the Angel Pharmacy Emanuel Merck takes over the Angel Pharmacy in Before this, his scientific education had taken him to the private institute of Johann Bartholomäus Trommsdorff in Erfurt, as well as to various universities. He was particularly fascinated by the chemistry of natural substances, especially alkaloids. The term is derived from the Arabic word al-qalw, meaning plant ashes, and the Greek suffix oid, which means like. These are chemically heterogeneous, usually alkaline organic compounds that contain nitrogen. They are produced from plants, animals or microorganisms and are highly effective for medicinal use. Morphine, derived from opium, is one of the best-known types of alkaloid.

13 13 Malachite from Johann Anton Merck s mineral collection

14 Shaping change [Everything possible must be done in order to] elevate the status of pharmacy from an empirical manual trade to a scientific art. Johann Bartholomäus Trommsdorff, Head of the Chemico-physical and pharmaceutical training institute, 1810 In the 19th century, the natural sciences experience a huge surge. Pharmacy develops from a manual craft into a science, and Emanuel Merck helps shape this development The pharmaceutical-chemical cabinet of curiosities The seed planted during his studies starts sprouting. In his pharmacy laboratory, Emanuel Merck continues working on natural substances. He eventually succeeds in preparing multiple kinds of pure alkaloids, which attract the attention of the scientific community due to their medicinal efficacy. In 1826, he publishes the results of his work on opium and morphine in the Magazin für Pharmacie. The presentation of the cabinet of curiosities in 1827 represents a milestone in the transformation from pharmacy handcraft to a research-based industrial company. He wants his collection of alkaloids and accompanying notebook to increase the general knowledge of this class of remedies [...] among chemists, physicians and pharmacists and to enable them to test these substances Business relationships across Europe Merck first establishes business relationships in other countries in Europe in the 1820s. In the business ledger from 1827, the customers listed include a certain Rudolf Geygy in Basel, and a few years later, customer relationships in Paris are documented Emanuel Merck and Friedrich Wöhler scientists sharing ideas When chemist Friedrich Wöhler needs substances for his research, Merck is his main contact. In 1843, Wöhler asks Merck for a few ounces of narcotin. In return, Merck receives urea crystals, which are a symbol of the paradigm shift in the world of chemistry: Wöhler had managed to produce urea from ammonium cyanate in Until that time, it had been considered impossible to produce an organic product from inorganic raw materials. The theory that an organic material needed a vis vitalis is thus disproved. Emanuel Merck is fascinated by this discovery, which will also benefit his own work.

15 Morphine from Merck the best quality Pharmacist assistant Friedrich Sertürner s work on the principium somniferum the sleep-inducing substance in opium - is finally accepted by the scientific community in Nevertheless, the reservations of doctors will long stand in the way of the powerful drug, called morphine after Morpheus, the Greek god of dreams, being used for therapeutic purposes. A high degree of purity is essential for effective therapy, and Merck sets the standard in this respect. Karl Friedrich Mohr, a professor of pharmacy in Berlin, writes the following in Comments on Prussian Pharmacopeia in 1849: I would prefer to take morphine from Merck than from an unknown manufacturer. Just as nobody is prevented from manufacturing permitted medicines, I don t want to see pharmacists being obliged to make medicines with which they have no experience. This is the case for morphine. Case for opium germanicum, 1833

16 Working together In 1850, I formed a business partnership with my two sons, Carl and Georg, with them assuming the role of associates with the same share in profit and loss in my pharmacy and factory business. The assets as stated initially are the property of the business partnership known as E. Merck Emanuel Merck, 1850 In order to ensure the continued existence of his company, Emanuel Merck establishes the partnership E. Merck (Geschäftssozietät E. Merck) together with his sons Carl and Georg. As of 1860, the youngest son Wilhelm becomes a partner as well. As businessmen, pharmacists, and chemists, the three brothers shape the company. The partnership is characterized by increasing staff numbers and the expansion of the product range. Now in the seventh generation of Merck ownership, the pharmacy transitions from an individual proprietorship to a company with multiple partners Guarantee of quality Emanuel Merck guarantees the quality of his products: In a letter to a customer, he writes: I guarantee you consistent purity of my preparations and will compensate you for any loss arising from an impure preparation. Numerous national and international distinctions prove Merck s sense of quality to be true Start of cocaine production In 1862, in line with the aim of making the major alkaloids available in their pure state, Merck starts offering cocainum hydrochloricum. When reports are published in 1884 on painless eye operations made possible through the use of cocaine anesthesia, demand greatly increases. Business records documented extraordinary interest among the scientific community. Willy Merck and Carl Emanuel Merck focus on the subject in their dissertations in 1886 and Starting in the 1880s, coca leaves from Peru are used to extract cocaine, and later, Kitz & Co. in Lima becomes a supplier of raw cocaine. By 1918, Darmstadt will have produced 67 metric tons of the ultrapure substance for research and medical purposes. As the negative effects of the substance become increasingly apparent, partial synthetic changes to the molecule are considered in the early 1920s to produce a more favorable effect profile.

17 17 Wilhelm Merck ( ), Georg Merck ( ) and Carl Merck ( )

18 Showing courage We must clearly understand that within the foreseeable future, the focus of our business will be here in America. America is the country of the future [and] will, perhaps when we are no longer alive, supply the world market with many of the products from our industry... Georg Merck, responsible for the U.S. business, 1897 Global expansion is indispensable for the future. Initial business relationships with Britain have existed since the early 1840s. There is evidently a representative office in 1871 and a branch in The sales organization is also successfully expanded at other locations. Own warehouses are set up in Paris, Brussels, Vienna, Budapest and Stockholm in order to respond to requests faster. Around 1900, Merck has business relationships on all continents Sydney International Exhibition At the exhibition in 1879, the company is represented with its own stand and is distinguished for its chemical and pharmaceutical products Establishment of an own representative office in New York E. Merck operates a successful export business to the United States, when there are increasing reports about counterfeit labels and inferior-quality products being sold under the famous brand. The good name is in jeopardy. The decision to establish an own branch for the sale of my excellent chemicals, alkaloids and pharmaceutical preparations is made quickly: in New York the gateway to the New World, in 1870 with around one million inhabitants and with a network of pharmacies run by German immigrants. Business is initially limited to the import of products from Darmstadt. The chemist Theodor Weicker is sent to New York as a delegate. However, owing to the complexity of tasks, it is soon found advisable to have the local presence of a family representative: In August 1889, Georg Merck and Theodor Weicker establish a trading company in New York One of the most successful moves One of the most successful moves which Merck has yet undertaken. Their American branch was hitherto constituted as an independent New York house but with all the partners of the home establishment at Darmstadt still interested in it. These words can be read in Oil, Paint and Drug Reporter in After Weicker and Merck founded a company in 1890 domiciled in New York under the name of Merck & Co., the business is publicly established in 1891 as a new branch. Nevertheless, close ties are still maintained with the parent company. The contribution by Georg Merck to the American company Merck & Co. is made available to him as a loan by E. Merck in Darmstadt. In return, Georg Merck, commits himself to transfer the amount that he on the basis of the New York company agreement will receive as a share in that company s profit, to the trading company E. Merck, Darmstadt, as it becomes due and payable, and without any deduction and to report from time to time on the progress and status of affairs of the New York company and make the inventories and balance sheets available to the company in Darmstadt. Furthermore, Georg Merck may not amend the company agreement of Merck & Co. in order to prevent the loan debt from being due and payable.

19 19 The company in Darmstadt commits itself to take over any loss that might accrue to Georg Merck and to pay a fixed annual compensation. Merck & Co. soon commences the direct customer business. In 1898, the very elegant and optimally equipped Merck Pharmacy is opened. This provokes the resistance of the so far best customers supplied by Merck other pharmacies. They fear aggressive competition, and pharmaceutical companies protest directly in Darmstadt. After two years, the ambitious company Merck Pharmacy has to be discontinued. The Merck Building in New York

20 showing courage 1888 Quality standards for reagents The testing of chemical reagents for purity by the Merck chemist Carl Krauch is the first standard work on chemical analysis to be published. It becomes the basis for Merck s guaranteed pure reagents labeled pro analysi ( for analysis ) now entering the market. Manufacture according to binding purity standards makes this the basis for comparative chemical analysis. Merck establishes a quality control laboratory to monitor its own high standards Start at the fermentation site the beginnings of biotechnology Today, biotechnology is defined as an interdisciplinary approach to research organisms, cells and their constituents as biological systems and to apply the findings. At Merck the biochemical toolbox of life finds early use. From 1893, lactic acid is produced from whey in a dairy in the Bavarian region of Allgäu. Documents mention a fermentation site at Merck in Darmstadt, where tests are already underway in Lactic acid is produced through a fermentation process. This development had been preceded by a bitter dispute among scientists about the nature of the fermentation process. Justus von Liebig ( ) saw it as a purely chemical process, whereas Louis Pasteur ( ) postulated that living cells were involved. Finally, it is Pasteur who discovers lactobacilli, thus enabling the first biotechnological production processes at Merck to take place Vaccines, sera, diagnostics: Research and innovations Merck establishes a department of bacteriology. Production comprises smallpox vaccine, diagnostics for tuberculosis and typhus, as well as sera for anthrax, streptococci, pneumococci and diphtheria. The diphtheria serum is a key research project: Hard work is done on making improvements to the process, which is soon crowned with success. Merck commercializes the serum in 100, 200 and 300-fold concentrations, based on defined units of immunization. Another breakthrough comes five years later. Merck gains a competitive edge when it develops a 1000-fold concentration of the serum Business in Russia Customers in St. Petersburg have been documented in the business ledgers since In 1898, branches and warehouses are established in St. Petersburg and Moscow. Price lists, brochures and E. Merck s annual reports on innovations in the fields of pharmacotherapy and pharmacy are published in Russian. All goes well until World War I causes major disruption. From 1921 onward, the Society for economic relations with the East and the German-Russian Association to cultivate and promote mutual trade relations are to revive business. However, in 1931, it is realized that there are no longer any ties whatsoever to the commercial representation of the USSR or to other official Russian procurement areas, and there seem to be no prospects for us to ever conduct business with Russia again.

21 A classic sleeping pill: Veronal In 1902, the chemist Emil Fischer and medical scientist Joseph von Mehring co-develop a sedative barbiturate, diethylbarbituric acid, which will replace the sleeping aids known so far. Fischer transfers the patent to Merck and production starts in At the same time, however, Bayer in Elberfeld is already working on an improved manufacturing process and the two companies agree to cooperate. Veronal s good tolerability without side effects ensures its success for decades. Ultimately, however, modern pharmacology identifies the problems of barbiturates, with their long after-effects and the risk of dependency. Production is ended in Veronal package, 1912

22 showing courage 1904 First list of finished medicinal products Due to the increasing complexity of obtaining and processing active ingredients, pharmaceutical production shifts more and more from pharmacies to factories. Merck publishes the first price list for finished medicinal products Liquid crystals In 1888, the Austrian botanist Friedrich Reinitzer discovers an unusual phenomenon. With help from the German physicist Otto Lehmann, he realizes that he has discovered a previously unknown state of aggregation. Lehmann introduces the name liquid crystals. Yet the physicist meets with adversity in the scientific community. He contacts Merck and asks for support. In 1904, the company begins selling high-purity substances with liquid crystalline properties. The professional world experiments with them and determines that Lehmann is right. However, a market for them will not develop until decades later First steps in the field of chromatography Today, chromatography is one of the most important analytical methods. In 1904, just one year after the Russian botanist Michail S. Tswett described the newly discovered separation principle for the first time, Merck starts the production of sorbents. Crucial to this is the contact to Hans Wislicenus, a chemist at the Royal Forest Academy of Saxony in Tharandt near Dresden. Successful cooperation results in the world s first industrially produced stationary phase for chromatography, an aluminum oxide for adsorption analytical purposes Community of interests Merck, Boehringer, Knoll, Gehe and Riedel An agreement to combine business operations is entered into by Merck, Boehringer, Knoll and Gehe, joined by Riedel in Advantages are to be derived from the joint procurement of raw materials and utilization of processes as well as streamlining the product range. This is in response to developments in the German chemical industry: The tripartite alliance (Bayer, BASF and Agfa) as well as the tripartite federation (Hoechst, Cassella and Kalle) call for a strong counterbalance. The basic principle is to maintain the individuality of each company, yet precisely this will lead to insurmountable difficulties. After World War I, the interests diverge to such an extent that the community of interests is dissolved again. In 1914, finished medicinal products are launched under the trademark MBK (Merck/Boehringer/Knoll), which are described in the first price list of January 1915 as reliable, convenient and inexpensive. The concept is an extraordinary success. The MBK brand exists until 1971.

23 Did Merck invent ecstasy? MDMA (3,4-methylenedioxy-N-methylamphetamine) has psychotropic and stimulating properties and can be therapeutically used in special cases. However, today the substance is known through its illegal use in the drug scene under the name ecstasy. False information is frequently spread concerning its origin and the role played by Merck in this connection. In 1912, Merck secures patent protection of a synthesis route for the hemostatic hydrastinine. The chemical formulation, which also describes ecstasy, is referred to in the patent merely as an intermediate product. The results of pharmacological investigations carried out in the 1920s and 1950s, when structurally similar compounds come into focus, indicate no meaningful use for the substance. The first publication on psychotropic effects of MDMA will not appear until 1978 in the United States at a time when Merck has long ceased to have anything to do with the substance. Tablet samples, around 1910

24 Living responsibility A company must not only pursue production and sales objectives, but also meet far-reaching social responsibilities. Willy Merck, partner in the company, on the occasion of the company s anniversary in 1918 The 250th anniversary of Merck is overshadowed by World War I; the years to follow are marked by dramatic changes. Yet important features remain the company s social responsibility, its ability to translate scientific advances into marketable products, as well as efforts to advance internationalization particularly in Latin America The fate of Merck & Co. As a consequence of World War I, Merck loses its subsidiaries abroad, including its American subsidiary Merck & Co., which becomes an independent U.S. company. In 1919, the company s stock is traded in the United States. With support from New York investors, George Merck reacquires his interest in a public auction. He becomes President of the public company Merck & Co. Today, Merck & Co. holds exclusive rights to the name Merck in North America, while Merck in Darmstadt holds the same rights in the rest of the world.

25 Crop protection A pest plague causes tremendous damage to the wine-growing regions of Germany and Austria. Merck responds with Dr. Sturms Heu- und Sauerwurmmittel for wine-growing. It is the first of a full range of plant protection agents for agriculture and forestry that the company will now begin developing Kohle-Compretten indispensable for treating poisons Since antiquity, powdered plant and animal carbon have served healing purposes owing to their pronounced adsorption properties. They are used to treat poisoning as well as festering wounds. In 1915, Merck offers Carbo animalis Merck for medicinal purposes for the first time. In 1924, Merck, Boehringer and Knoll commercialize Kohle-Compretten under the MBK brand. As of 1939, Merck markets Ultracarbon, which is another carbon product, and Ultracarbon granules are approved in Today, medicinal charcoal is derived exclusively from coconut shells and is used to treat diarrhea and acute oral poisoning Besides light and cleanliness, the best thing is Vigantol Merck and Bayer co-market the first standardized vitamin D product. Vigantol is urgently needed to treat rickets at the time still a common deficiency disease, particularly among children. Following the success of Vigantol, Merck manufactures additional vitamins that are derived from natural raw materials or synthesized. Shipment of crop protection agents, 1925

26 living responsibility 1933 First production of iridescent products In the 17th century, Essence d Orient a suspension prepared from shiny, silvery fish scales is sold as an expensive essence to make fake pearls. Bismuth oxychloride from shiny scales is used as Blanc de Perle as a basic ingredient for cosmetics up until the 1920s. People seem to have a need for iridescent pigments with a mysterious shine. In 1933, Merck commences initial manufacturing trials which do not yet fully satisfy the demand of inquiring customers. In 1936, nearly 3,000 kilograms of a product based on lead phosphate are produced. The search for non-toxic, easy-to-process and nevertheless magnificent substances begins, yet does not lead to a milestone in the Pigments business until almost 40 years later, with the use of natural mica Vitamin C for all Among the vitamins that Merck manufactures from natural raw materials or synthesizes itself is ascorbic acid, which is commercialized as the first vitamin C product under the name Cebion in As proposed by Albert Szent-Györgyi, who would later win the Nobel prize for medicine, Cebion is initially extracted from gladiolas and sweet peppers; later on it will be synthesized. Ascorbic acid successfully eliminated scurvy, the classical vitamin C deficiency disease of former centuries, and is widely used today not only in medicine, but also in the food industry. Nursery school excursion, 1941

27 Childcare at Merck As the issue of women working now presents a problem in totally different light than just a few years ago, as of 1940 children from the ages of six weeks to six years are cared for at the E. Merck nursery school headed by the site social welfare staff. Exemption from fees in special circumstances, medical support and the problem of attaining sufficient places are important issues at the time.

28 living responsibility 1942 Factory work during World War II Almost 1,000 employees are conscripted into the German army at the end of In order to address the labor force shortage, attempts are initially made at encouraging more women to do factory work. This meets with little enthusiasm particularly since, as reported in one issue of the employee newspaper, a social allowance is no longer granted to husbands whose wives are working. Soon French prisoners of war and foreign civilian laborers also help boost the labor force. In early 1942, it is reported by Italian laborers who as a contemporary witness recalls were given the choice back in their home country of either becoming a soldier or going as a laborer to Germany. Some laborers from the Flemish part of Belgium are recruited to Darmstadt by Merck. In 1942, the first laborers arrive from occupied parts of Eastern Europe. Until the end of the war, 257 Russians and eight Poles, mostly women, come to Merck as forced laborers. On the drill ground in Darmstadt, a communal camp is set up for about 550 laborers from Eastern Europe to work for the needs of the city, but also of industry. In December 1942, the first 63 of Merck s Eastern laborers move from the camp in Griesheim to the communal camp. In March 1943, the first barracks are set up at the company site for 157 Eastern laborers. The National Socialist leaders use threats of strict punishment in an attempt to combat the danger of the German population integrating with the laborers from across half of Europe. At Merck for example, too, an appeal is made particularly to the younger, female loyal followers to stay away from the foreign laborers Death and destruction Sixty employees die in a targeted air raid on the factory in December Over 200 explosive and incendiary bombs land on the company site, destroying most of the buildings. Nevertheless, production continues partly outdoors. On March 25, 1945, American troops occupy the company site.

29 29 The destroyed Angel Pharmacy, 1944

30 Tackling new challenges together It did not appear as though the company could operate in the global market again in the foreseeable future. Contemporary witness, 1946 Research and development work forms the basis for Merck s growth. In addition, Merck succeeds in reacquiring some of the subsidiaries it had lost in World War II, such as in Spain and in Central and South America. Merck regains a foothold in other European countries as well. With Iran-Merck, the company ventures to operate in a country that is transforming from a developing country into an emerging industrial economy Export business with bureaucratic hurdles The Marshall Plan and the currency reform visibly revive the post-war economy. The economic miracle lasts until the mid-1960s. Merck already resumes its export business in To start with, there are considerable bureaucratic obstacles to overcome: For each order, six forms are required in 22 copies each.

31 31 Export business a synonym for permanent communication. It is the task of women to handle this professionally.

32 tackling new challenges together 1949 Digitoxin Merck is launched The use of the foxglove plant digitalis for dropsy or edema, meaning the clinical picture of heart failure, is already described in detail in However, before the ingredients are isolated and tested during the 19th century, it is virtually impossible to achieve effective yet safe dosage of the plant preparations. In 1857, the Merck price list already includes Digitaleinum and Digitalinum. But scientists will work for decades in order to offer a standardized active form. As of 1949, Digitoxin Merck known as Digimerck since 1953 becomes an indispensable cardiology drug Pec and the cough medicine Pectamed Pectamed comes to the rescue when Pec, the cough monster, has been at work. This is a rough translation of the motto used to launch the cough medicine Pectamed in The star of the advertising campaign is Pec, the cough monster, who blows infectious germs onto unsuspecting people. The humorous advertisement meets with great interest; sales of the product grow steadily.

33 33 Advertisement for the cough medicine Pectamed, 1953

34 tackling new challenges together 1955 Modern-technical microbiology biotechnological steroid syntheses In the early 1950s, corticoids are a highly topical research field and hope for many patients. Merck acquires licenses for a microbiological process to manufacture prednisone and prednisolone. This and the start of extensive synthesis work make it necessary in 1955 to build up modern fermentation technology. Help from microbiological reactions are to enable targeted changes to complex molecules. The necessary methods are developed on a laboratory and pilot plant scale in close interdisciplinary cooperation among microbiologists, process engineers and chemists. Developments in Germany take place exclusively in industry at Schering and at Merck. Between 1959 and 1970, Merck is granted 34 patents in Germany involving the use of biotechnology Growing older with Gerobion Gerobion is the first vitamin combination product for geriatric health. Gerontology plays an increasingly important role as of the mid-1950s The Merck sche Kindertagesstätten-Verein (Merck daycare center association) is established The site nursery school founded in 1940 was closed at the end of World War II. At the end of the 1960s, as Germany nears full employment and consequently faces a shortage of labor, there is a growing need for and acceptance of women in the workforce. Merck therefore decides to re-establish a company-own daycare center. In 1967, the Merck family sets up the Merck daycare center association under the chairmanship of Barbara Groos. In 1969, a crèche, a nursery school and a daycare center (for schoolchildren) is opened with capacity for 80 children. The model character of the new center, which is constantly updated, is praised over the decades as are the company s initiatives to create equal opportunities for men and women in the workplace.

35 35 Histological cross-section of brain tissue

36 Thinking strategically a fearful medium-sized company was transformed into a global corporate group. manager magazin 6/2007 on electing Hans Joachim Langmann to the Hall of Fame The transformation into a successful international corporate group can first be seen in the steady expansion of the network of subsidiaries and affiliates abroad. Yet a great deal is also done for employees. Structural changes are the reaction to the growing capital requirements stemming from the growth process. For instance, the company goes public in India in The most important turning point comes in 1995 with the foundation of Merck KGaA and the issue of shares that are traded on the stock exchange Revival of liquid crystals In the late 1930s, interest in liquid crystals had vanished due to a lack of technical application possibilities. A long Sleeping Beauty slumber begins and lasts until the end of the 1960s, when Merck resumes research work owing to impetus from the United States. With the first liquid crystal displays, the dream of flat-panel televisions that hang on the wall like pictures is born. In 1980, the company already establishes a laboratory for liquid crystal mixtures in Atsugi, Japan in order to be closer to customers in Asia. In 2003, Merck researchers receive the German Future Prize from the President of the Federal Republic of Germany for their project entitled Lighter, faster, brighter: liquid crystals for television screens.

37 37 The theory of functioning displays

38 thinking strategically 1969 Cold treatment Nasivin on the moon On July 21, 1969, Apollo 11 accomplishes the highlight of its mission: Neil Armstrong and Edwin Aldrin are the first men to set foot on the moon. Intensive research is conducted beforehand into the effects of weightlessness on the human body. The astronauts have to be kept under special medical observation on their trip to the moon. NASA (National Aeronautics and Space Administration) provides an on-board pharmacy of carefully selected medicines against any disorders that could compromise the success of the mission. Since weightlessness is known to cause the nasal mucous membranes to swell, it is absolutely essential to have a decongestant on board. Contrary to the recommendation, for reasons of space they initially do without a decongestant on the mission with almost fatal consequences: The crew of Apollo 7 suffer from blocked noses to such an extent that they cannot close the helmets of their spacesuits during re-entry into the Earth s atmosphere. NASA now equips its space missions with oxymetazoline developed by Merck (known as Nasivin in Germany). This decongestant becomes an integral part of the medical kit of the Apollo missions and lunar modules and is also on board the space shuttles. The substance is selected owing to its rapid onset of effect, which lasts up to 12 hours, and its excellent tolerability. Recent investigations have demonstrated antiviral and anti-inflammatory properties Experimental drug research The requirements for new drug development increase. Methods with which newly developed substances are tested become increasingly sophisticated, sensitive and complex. Regulatory authorities around the world call for increasingly comprehensive and detailed documentation when submitting a new drug for approval. Merck responds by establishing the Institute for Experimental Drug Research in Grafing near Munich. Drug substances are labeled using special chemical techniques and tested in a maximum number of organ systems with state-of-the-art equipment Aconcen A product for contraception according to doctor s orders becomes the target of criticism Merck also conducts extensive research work and, in 1964, commercializes the combination product Aconcen for contraception according to doctor s orders. The public debate for and against manipulating a woman s body with the pill is conducted not only for medical reasons. Since the Contergan affair, the focus is especially on the potentially serious side effects of drugs. In 1970, warning notifications are received from the United States. Although statements by the scientific community are contradictory, Merck withdraws Aconcen from the market in Drug safety has top priority. Although the fears prove to be unfounded Merck never re-enters the sex hormone market.

39 39 The face of Aconcen advertising

40 thinking strategically 1970 Pearl effect pigments based on mica Merck makes a key breakthrough in the production of pearl effect pigments for universal applications in From extensive work already conducted, it is known that the monocrystalline, white pigment titanium dioxide flakes would in many respects make an ideal pearl effect pigment: its light resistance, toxicological safety and chemical resistance are superb. However, it is not possible to produce the titanium dioxide as flakes. While seeking flake substrate onto which the pigment could be applied in a thin layer, the highly abundant mineral mica is discovered as a possible solution. The coating of this inert material produces excellent results another milestone for pigment research at Merck Diabetes as a therapeutic area Research continues to be the basis for product development. In the early 1990s, the treatment of type 2 diabetes becomes an important therapeutic area with the global blockbuster Glucophage Mission Statement The global Mission Statement, formulated in 1991, defines Merck s self-image as a successful and responsible company. It also expresses the objectives, which are targeted to the interests of customers, providers of capital, employees and society. One of the core principles of the Mission Statement is: Entrepreneurial success starts with people. Our goal is to operate a worldwide business that produces meaningful benefits for consumers, our market partners and our community Merck KGaA is formed The sustained growth process and the related increase in demand for capital are accompanied by structural changes. Merck KGaA, a corporation with general partners, is founded in With a volume of DM 2.4 billion, this represents the largest public offering in German history at that time. Merck KGaA manages the operating business of the Merck Group. The Merck family owns a majority interest in Merck KGaA via the general partner E. Merck KG.

41 41 Mica: Natural basis for pearl effect pigments

42 today Unlocking potential Innovations are successfully implemented new ways of doing anything that creates value for Merck or our customers. Karl-Ludwig Kley, Chairman of the Executive Board of Merck, A new brand design Over the centuries, the company and the environment, and thus the trademark, change considerably. Yet a complete break with the past never occurs at Merck. In contrast to newly created corporate groups, Merck enjoys a special feature of continuity: the Merck family of owners. The fact that this is reflected in the continuity of the Merck brand is a logical consequence, even though two companies with the same name have existed since the separation of Merck & Co. during World War I. The links to tradition are unmistakable, even in territories where Merck is not permitted to use the name. The EMD lettering, which has been used as the umbrella brand for all Merck activities in North America, stands for Emanuel Merck, Darmstadt patent protected for the first time back in Yet in order to achieve a visual link between the EMD and Merck brands, the graphic elements have been added to the name. A major objective of the redesign in 2001 is to unite subsidiaries and affiliates around the world under one umbrella brand. Long-lasting expansion with many acquisitions and greater public interest since the public listing are the reasons for the redesign of the Merck brand Erbitux for the treatment of various forms of cancer In the mid-1980s, the foundations for Merck s own oncology research are laid. At the end of 2003, the active ingredient cetuximab is approved as Erbitux for the treatment of colorectal cancer. The monoclonal antibody binds and blocks epidermal growth factor receptor (EGFR). EGF receptors are found on the surface of cells of many turmors and stimulate cell growth and division when activated by growth factors. Erbitux blocks these receptors, which interferes with tumor growth and in some cases even makes the tumor shrink. Merck licensed the marketing and development rights to Erbitux outside of the United States and Canada from ImClone Systems in In Japan, Merck shares the exclusive marketing rights with ImClone (now a 100% subsidiary of Eli Lilly) and Bristol-Myers Squibb. Erbitux ranks among the most successful oncology product launches in Europe Divestment of the Electronic Chemicals business Merck sells its Electronic Chemicals business for 270 million to BASF AG in agreement with the corporate strategy of focused diversification, concentrating on innovation-driven and sustainably profitable businesses within pharmaceuticals and chemicals.

43 Divestment of the Generics division Merck sells its Generics business for 4.9 billion to Mylan Laboratories Inc, Canonsburg, Pennsylvania, USA. The transaction enables Merck to focus on the further growth of research-driven specialty businesses in pharmaceuticals, chemicals and life science. Merck uses the proceeds to reduce net financial debt. In 2006, the Generics division generated sales of 1.8 billion and had nearly 5,000 employees. The Merck brand

44 today unlocking potential 2007 Advancing to the premiere league of Deutsche Börse Following the meeting of its Stock Index Working Group, Deutsche Börse AG announces on June 5 its decision: Merck KGaA will be admitted to the DAX 30 Index. As of June 18, Merck shares become part of the DAX Merck Serono is established With the transformational acquisition of Serono for a purchase price of 10.3 billion, Merck becomes a leading biotech company and makes the largest acquisition ever in the company s history. It is no secret that Merck wishes to strengthen its business in pharmaceuticals. Merck attempts to acquire Schering in 2006, yet in a bidding war, Bayer prevails. Shortly afterwards, Merck surprisingly offers to acquire Serono S.A. The Geneva-based biotech company, which is run by the Bertarelli family and has around 5,000 employees, meets the requirements of the corporate strategy: achieving a critical mass in research and development, strengthening the research pipeline as well as the product portfolio, and improving the company s presence globally, especially in the United States and Japan China: Four subsidiaries and three representative offices Merck has a long tradition in China with officially documented business contacts dating back to 1897/1898. Yet repeated setbacks occur. Therefore, it takes until 1997 before E. Merck (Shanghai) Trading Co., Ltd. (MESC) becomes the first Merck company to be established in China after World War II. It takes a further ten years Merck is meanwhile represented by four independent legal entities and three representative offices for a self-confident and successful expansion to begin, for instance with the opening of the first liquid crystals application laboratory in In 2012, China generated around 5% of Group sales.

45 45 The new headquarters of Merck Serono China on Gemdale Plaza Beijing, 2008

46 today unlocking potential 2009 Merck wins family business excellence award Merck is the winner of the 14th IMD Lombard Odier Global Family Business Award. It is considered the Nobel prize for family companies and recognizes global business activities, exemplary corporate governance, the involvement of multiple generations as well as the uniqueness and sustainability of social commitment. Merck, the world s oldest pharmaceutical and chemical enterprise, is an extraordinary example of long-term leadership which has adapted to geopolitical changes and competitive global environment for 341 years and 12 generations. The harmonious balance of family values, exemplary governance and business performance drives the long-term success of the company, said IMD President John Wells Acquisition of Millipore With the acquisition of the Millipore Corporation, a leading life science company based in Billerica, Massachusetts, USA, Merck continues with its strategy of focusing on highly profitable specialty products with attractive growth rates. Additionally, the acquisition leads to a more balanced relationship between pharmaceuticals and chemicals at Group level. The aggregate purchase price including debt and cash is approximately 5.2 billion. In 2009, Millipore generates sales of US$ 1.7 billion with around 6,000 employees in more than 30 countries Successful donation program to fight schistosomiasis Schistosomiasis is the most common tropical disease in Africa after malaria. More than 200 million people suffer from the worm disease; more than 200,000 of those infected die each year of its consequences. The consequences are particularly serious among children. Schistosomiasis stunts growth, causes learning disabilities and leads to anemia. In 2007, Merck enters into a partnership with WHO to combat schistosomiasis primarily in African school children. The program is called the Merck-Praziquantel Donation Program. Originally, the program was scheduled to end in At the end of 2011, Merck decides to continue its efforts indefinitely. The joint goal with WHO is to eliminate the disease in Africa. Since the program began, Merck has donated more than 100 million tablets to treat over 28 million children The Merck Values: Basis for success With around 39,000 employees, Merck is represented today in 67 countries around the world. With strong businesses and brands in pharmaceuticals, chemicals and life science, Merck generated total revenues of more than 11 billion in The basis for our entrepreneurial success are the six Merck Values communicated in 2007: courage, achievement, responsibility, respect, integrity and transparency. These values govern our entrepreneurial actions, for instance our dialogue with customers and business associates as well as the way we cooperate with each other inside the company.

47 47 A Merck Millipore bioreactor