A fascinating story of the discovery & development of biologicals for use in clinical medicine

Abstract

A young physician starting a fresh career in medicine in this millennium would hardly stop to think about the genesis of a particular biological drug that he/she will be prescribing for a patient evaluated in the morning outpatient department. For him/her, this is now routine, and the question of 'Who', 'How' and 'When' about these biologicals would be the last thing on their mind. However, for those who came to the medical profession in the 1950s, 1960s and 1970s, these targeted drugs are nothing short of 'miracles'. It would be a fascinating story for the young doctor to learn about the long journey that the dedicated biomedical scientists of yesteryears took to reach the final destination of producing such wonder drugs. The story is much like an interesting novel, full of twists and turns, heart-breaking failures and glorious successes. The biologicals acting as 'targeted therapy' have not only changed the natural history of a large number of incurable/uncontrollable diseases but have also transformed the whole approach towards drug development. From the classical empirical process, there is now a complete shift towards understanding the disease pathobiology focusing on the dysregulated molecule(s), targeting them with greater precision and aiming for better results. Seminal advances in understanding the disease mechanism, development of remarkably effective new technologies, greater knowledge of the human genome and genetic medicine have all made it possible to reach the stage where artificially developed 'targeted' drugs are now therapeutically used in routine clinical medicine.

Keywords: Biological drugs; drug discovery; history of medicine; infliximab; monoclonal antibody; tumour necrosis factor-α.

Fig. 1

Dr Jean-Michael Dayer (Photograph personally provided for use in this article).

Fig. 2

Dr Anthony (Toni) Cerami (Photograph personally provided for use in this article).

Fig. 3

Dr Bruce Beutler (Courtesy: Brian Coates for UT Southwestern medical Center).

Fig. 4

Dr Jan Vilček (Photo credit: Peter Hurley, provided by Dr Jan Vilček personally for use in this article).

Fig. 5

Dr Bharat Bhushan Aggarwal (Photograph personally provided for use in this article).

Fig. 6

Dr Brigitte Ita Askonas (Courtesy: Sir Marc Feldmann, and reproduced with permission from Eur J Immunol).

Fig. 7

Dr Niels K. Jerne [The photograph kindly provided by Prof. Thomas Söderqvist; it is also published in the biography of Jerne: Science as Autobiography (Yale University Press, 2003)].

Fig. 8

César Milstein and Georges JF Köhler (Kindly provided by Ms Celia Milstein for use in this article).

Fig. 9

Sir Ravinder Nath Maini and Sir Marc Feldmann (Courtesy: Sir Marc Feldmann and reproduced with permission from The Lasker Foundation).