The History of Biologics: Problems, Perseverance, and Potential

The usage of biological products is as old as medicine itself, as humans have been using plant and animal products to treat disease for thousands of years. Even modern concepts like vaccination date back hundreds of years – with inoculation against smallpox using powdered scabs being practiced in China as early as the 10th century.1 But it was not until the early 20th century – and the advent of synthetic pharmaceuticals – that the production and usage of biologics was recognized as distinct and the term biologics first emerged in the lexicon. During this period, biologic-derived products such as vaccines, sera, and vitamins began to be mass-produced, resulting in a scramble to standardize their definition, production, and quality – ultimately culminating in the Biologics Control Act enacted by the United States Congress in 1902.2

The number and variety of biologics continued to grow through the course of the 20th century, as did the capacity to produce these agents. Perhaps most importantly, this period witnessed the first successful usage of an in vitro system to produce biologics when Boston Children’s Hospital researchers produced Lansing Type II polio virus using a human tissue cell culture in 1949 – a development that would set the stage for modern biologics production.

A genetic revolution

The advent of genetic engineering during the late 1970s and early 1980s opened up new avenues for biologics production and development.2 The ability to modify genetic sequences meant that researchers could modify existing agents to improve their stability, safety, and/or efficacy. These alterations could also be used to change agent targeting specificity, giving certain agent types, such as antibodies, a significantly greater range of applications. Finally, genetic engineering gave researchers a considerably larger portfolio of potential production models to work with. Whereas establishing a cellular factory was previously limited by the genome of the production cell – or, in the case of viral production, its susceptibility to persistent but non-lethal infection – the emergence of transfection and transduction now meant, in theory, that any cell could be made to produce any molecular/protein-based agent.

The integration of genetic engineering techniques with biologics development and production marked a transition point in the history of biologics. The historical definition of biologics as natural agents – in contrast to synthetically derived counterparts – shifted towards a more nuanced interpretation: biologics were now agents with natural components or origins that were either constructed or produced with the assistance of bioengineering or biotechnology.2

Working with nature: new molecules, new cells, new systems

Biologics research and production has seen tremendous growth since the 1980s, with considerable progress made in the development of new therapeutic approaches for cancers, immune disorders, and rare genetic disorders, just to name a few.3 A field that once was simply the extraction of naturally produced substances has evolved to encompass the conception, engineering, and production of a diverse range of sophisticated designer molecular-, protein-, gene-, cell-, and tissue-based agents capable of highly-selective targeting. Certainly, challenges still remain with regard to efficacy, specificity, and longevity, but science – and scientists – are continually working towards discovering and developing new agents and tweaking existing ones.4

  1. C.P. Gross and K.A. Sepkowitz, “The myth of the medical breakthrough: smallpox, vaccination, and Jenner reconsidered,” Int J Infect Dis, 3(1):54-60, 1998.
  2. A. von Schwerin et al., “Biologics: an introduction,” in Biologics, a History of Agents Made From Living Organisms in the Twentieth Century, A. von Schwerin, H. Stoff, B. Wahrig, ed., London: Pickering & Chatto, 2013, pp. 1-33.
  3. L. Andrews et al., “A snapshot of biologic drug development: Challenges and opportunities,” Hum Exp Toxicol, 34(12):1279-1285, 2015. 
  4. N. Casadevall et al., “Evolution of biological agents: how established drugs can become less safe,” BMJ. 357:j1707, 2017. 
Helpful Links