“Non-chemical” drugs: biologicals, protein therapeutics, vaccines and antisense therapeutics

Abstract

It has long been recognized that living organisms have an astonishing ability to develop biochemical survival strategies [1]. One example for such a strategy is the mammalian immune system — an adaptive response to evolutionary challenges by microorganisms. In the past, numerous attempts have been made to exploit these endogenous “biological” survival strategies for medicine. One of the first successful attempts to employ a “biological” in this regard was the introduction of the variola vaccine by Jenner in 1796, at a time when the armamentarium of traditional chemical drugs had been notoriously poor. In the beginning of the 20th century, however, a revolution in chemistry and pharmacology overshadowed the “biological” by a “xenobiotic” concept and led to an explosion of our therapeutic options by providing the more than 10,000 traditional chemicals that we employ in medical practice today. Although our 100 years of experience with traditional chemicals have proven extremely successful, major challenges to our current drug development strategies have arisen by concerns about side effect profiles of many drugs and a perceived reduction in research productivity [1, 2]. Since the dawn of the 21st century we have witnessed the long expected and increasingly successful implementation of biotechnology derived pharmaceuticals (“biologicals”) in the medical practice. The term “biotechnology” was allegedly coined by Karl Ereky, a hungarian engineer in 1919 and related to techniques that had been employed by mankind for thousands of years to produce improved food products e.g. beer by the Sumerians as early as 6000 B.C. In contrast to the more traditional small molecular chemicals, biologicals are derived from living organisms like bacteria, yeast or even larger animals like goat or cow. Biologicals comprise a heterogenous group of pharmaceutical products, notably blood products, recombinant proteins, gene therapeutic products and cellular products. Due to their specific characteristics, biologicals introduce major challenges to our traditional concepts of drug development and routine practice of therapeutic medicine. Biologicals can be distinguished from traditional chemicals by a number of unique features, e.g. molecule size, low thermostability, species specificity and mode of administration. Therefore, biologicals do not only constitute novel pharmaceutical agents but represent an entirely different class of drugs which, unlike chemicals, do not follow well established paths, both in development and in practical use.