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  • The Lock and Key of Medicine: Monoclonal Antibodies and the Transformation of Healthcare by Lara V. Marks
  • Carsten Timmermann (bio)
The Lock and Key of Medicine: Monoclonal Antibodies and the Transformation of Healthcare. By Lara V. Marks. New Haven, CT: Yale University Press, 2015. Pp. xxv+ 316. $40.

Specificity is the essence of biomedicine. Much modern biomedical research is concerned with investigating the mechanisms of life, with the declared goal of developing specific repairs for any defects in such mechanisms, or finding substances that kill malicious intruders identified as causes of human disease. More than a hundred years ago the German bacteriologist Paul Ehrlich used the metaphor of the magic bullet to characterize his vision of such substances: they would miraculously find their target without causing collateral damage. By the 1980s many believed that the new monoclonal antibody (Mab) technology finally provided humankind with a means of creating such magic bullets. Mabs were expected to revolutionize both the diagnosis and the treatment of many diseases. And indeed, as Lara Marks shows in The Lock and Key of Medicine, by 2012 ten drugs based on monoclonal antibodies had achieved blockbuster status, generating profits of $1 billion or more each. Mabs have found uses in the treatment of cancer as well as conditions such as rheumatoid arthritis and Crohn's disease. Essential components of pregnancy tests as well as diagnostic kits for infectious diseases, they have also transformed diagnostics.

Marks's book tells the story of Mab technology from its humble beginnings in César Milstein's lab at the UK Medical Research Council's Laboratory for Molecular Biology in Cambridge to their present day. Milstein, along with two other Mab pioneers, Niels K. Jerne and Georges J. F. Köhler, was rewarded with a 1984 Nobel Prize for his efforts. However, in 1975, when they first described the method, it was far from obvious that these efforts would be crowned by commercial success. In fact, commercial success was not what Milstein and his colleagues had on their minds—initially the method was not patented and they shared their Mabs freely with colleagues elsewhere. To the pioneers, Mabs were a promising laboratory tool, more reliable than the conventional antisera that differed from batch to batch. Conventional antisera were mixtures of different antibodies that animals such as sheep or horses generated against a particular antigen (for example a biological molecule). Monoclonal antibodies against the same antigen were homogeneous and could be produced in unlimited amounts. Once generated and characterized, these antibodies could then be chemically linked, for example, to radioactive or fluorescent substances, or chromatography columns, and used to label or purify biological molecules in a wide variety of samples. This was the exciting theory, but in practice it was complicated, as this fairly technical book shows convincingly.

While Milstein and his colleagues were not overly interested in making [End Page 1105] money, others did realize the commercial potential of Mabs. In a fun chapter on the "Wild West of Antibody Commercialization," Marks tells the story of David Murray, an engineer who enrolled to study biology in the United States until called back to the United Kingdom to save his father's Soho nightclub business from bankruptcy. In 1968 they fell out and Murray bought a dilapidated country house with some land, where he started to breed rabbits for research, later diversifying into antiserum production. In 1977 he met Milstein and, realizing the potential of the new technology, his company Sera-Lab moved into the commercial production of Mabs for research. Marks compares the strategies of Sera-Lab with other start-ups involved in the commercialization of Mabs, such as Hybritech in San Diego or Centocor in the Philadelphia area. All had to rely on collaborations with established pharmaceutical companies, who may have been slower to realize the potential of the new technology but had the sales force, financial stamina, expertise in organizing clinical studies, and experience with the regulators. That said, some of these established companies may have had as much vision as the new kids on the block. The future Nobel laureate Georges Köhler, for example, after leaving Cambridge in 1974, spent nine years of his career at...

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