S4.E8. 全面啟動：基因工程

Rolf G. Werner博士（Prof. Dr. Dr. Rolf G. Werner）不只是一位夢想家，也是一位造浪者。早在1980年代初期，Werner博士就在德國比伯拉赫（Biberach）創建了百靈佳殷格翰的生物製藥基地，以此為出發點，逐步往歐洲、美國、中國發展。

翻轉未來的關鍵籌碼

Werner博士在1983年就說服公司的管理階層投資了7700萬歐元，在比伯拉赫（Biberach）成立一家當時全球最大的生物製藥工廠，這在整個歐洲跟百靈佳殷格翰都是過去前所未見的創舉。Werner說，他常常站在工地現場，擔心著：「一切都能順利進行嗎？」。由細胞培養的生物製藥將會為難以治療的疾病帶來突破性的發展，生物反應器（bioreactor）因此成為翻轉未來的關鍵籌碼；但在當時，生物製藥尚未在德國取得許可。

身為非常傳統的施瓦本人（Swabian），Werner的做事風格非常謹慎；但只要確認了目標，他就會拋下所有的遲疑，勇敢前行。在1980年代中期，雖然Werner只是百靈佳殷格翰與加州生技公司Genentech合作項目的專案經理，卻勇於做夢，並且堅持這樣的理念：「若要開發能『治本』的藥物，基因工程是下一個合理並富有邏輯的步驟」。來自德、美兩國的夥伴齊心在比伯拉赫的製藥基地鑽研細胞培養，希望能產出生物製藥活性成分（biopharmaceutical active substances）。他們因此拓展出一片新天地，Werner說：「那時候的百靈佳殷格翰只是一間化學製藥公司」，在生物化學家跟基因工程師的加入後，局勢開始變化。

推動社會與法律的改變

然而，最大的阻力始終來自於外部環境。Werner回憶說：「長期以來，社會大眾對基因工程藥物充滿懷疑。」Werner造訪許多間成人教育機構，很有耐性地回答市民的提問，希望能撫平大家的焦慮；他說：「基因研究會為患者帶來的益處，是我最強而有力的辯論工具。」

但困難與挑戰並不止於此：德國的基因工程法規必須修正，才能因應生物製藥的發展。Werner團隊與德國化學工業協會（German chemical industry association，簡稱VCI）共同扮演推手的角色；到1990年，德國聯邦議院（Bundestag）終於做出改變，生物製藥終於能在正確的軌道上推進。

這些都只是「成功的故事」的前情提要。比伯拉赫的300名團隊成員進而開始拓展他們的業務範圍；如今在全球四個國家共有約4000名同仁，規模與人數依然持續成長中。百靈佳殷格翰如今已研發出35種以上的生物製劑，供世界各地的患者使用。

A pioneer twice over

Prof. Dr. Dr. Rolf G. Werner is a visionary and pioneer. He established the company’s biopharma site in Biberach, Germany, in the early 1980s and paved the way for its Biopharmaceutical Contract Manufacturing in Europe, the US and China.

In 1983, Rolf G. Werner was trying to convince the company’s management to invest in a pi lot facility in Biberach for the manufacturing of biopharmaceuticals – the first of its kind in Europe and at Boehringer Ingelheim. The construction of what was then the world’s newest and largest bio technology facility cost the equivalent of around 77 million euros – a huge amount at the time. Werner frequently found himself standing at the construction site, worrying “Will it all work out?” The bioreactors represented a bet on the future: Biopharmaceutically produced medicines from cell cultures would provide a breakthrough for diseases that were difficult to treat. But such biopharmaceuticals had not yet been approved in Germany.

Werner acts cautiously and deliberately – he’s a typical Swabian. But when he’s convinced of something, he casts restraint aside. “When it comes to the development of medicines that are intended to eliminate the causes of a disease, genetic engineering is the next logical and rational step.” Werner was convinced of that in the mid1980s, when he was the project manager for Boehringer Ingelheim’s partnership with Californian biopharmaceuticals company Genentech. In Biberach, Germans and Americans worked together on cell cultures to produce biopharmaceutical active substances. They were breaking new ground within the company. “Back then, Boehringer Ingelheim was a chemical and pharmaceutical company,” says Werner. Things had changed for the company’s chemists now that biotechnologists and genetic engineers also had a seat at the table.

In any case, the greatest resistance existed outside the plant. “For a long time, the public opposed genetically engineered medicines,” Werner recalls. He visited adult education centers and patiently answered citizens’ anxious questions, of which there were many. “My strongest argument was always the benefit of genetic research for patients,” Werner explains.

Yet that was by no means the end of the difficulties: It was necessary to revise Germany’s genetic engineering act to reflect biopharmaceutical progress. Together with the German chemical industry association (VCI), Werner and his team pushed forward with these changes. In 1990, Germany’s Bundestag resolved a change in the law which created the right framework for biopharmaceuticals.

They thus laid the foundations for a success story. The 300 team members in Biberach became a business area that has around 4,000 employees at four locations worldwide – and continues to grow. Boehringer Ingelheim has now produced more than 35 different biopharmaceutical medicinal products used by patients around the world.