The Drug development process - Pharmaceutical Biotechnology: Concepts and Aapplications - page 61

regulatory molecule. Other diseases, however, may be multifactorial and, hence, more complex.
Examples include cancer and infl ammation. Nevertheless, cytokines, such as interferons and in-
terleukins, known to stimulate the immune response/regulate infl ammation, have proven to be
therapeutically useful in treating several such complex diseases (Chapters 8 and 9).
An understanding, at the molecular level, of the actions of various regulatory proteins, or the
progression of a specifi c disease does not, however, automatically translate into pinpointing an
effective treatment strategy. The physiological responses induced by the potential biopharmaceu-
tical in vitro (or in animal models) may not accurately predict the physiological responses seen
when the product is administered to a diseased human. For example, many of the most promising
biopharmaceutical therapeutic agents (e.g. virtually all the cytokines, Chapter 8), display multiple
activities on different cell populations. This makes it diffi cult, if not impossible, to predict what
the overall effect administration of any biopharmaceutical will have on the whole body, hence the
requirement for clinical trials.
In other cases, the widespread application of a biopharmaceutical may be hindered by the oc-
currence of relatively toxic side effects (as is the case with tumour necrosis factor

,
Chapter 9). Finally, some biomolecules have been discovered and purifi ed because of a character-
istic biological activity that, subsequently, was found not to be the molecule's primary biological
activity. TNF-α again serves as an example. It was fi rst noted because of its cytotoxic effects on
some cancer cell types in vitro . Subsequently, trials assessing its therapeutic application in can-
cer proved disappointing due not only to its toxic side effects, but also to its moderate, at best,
cytotoxic effect on many cancer cell types in vivo . TNF's major biological activity in vivo is now
known to be as a regulator of the infl ammatory response.
In summary, the 'discovery' of biopharmaceuticals, in most cases, merely relates to the logical
application of our rapidly increasing knowledge of the biochemical basis of how the body func-
tions. These substances could be accurately described as being the body's own pharmaceuticals.
Moreover, rapidly expanding areas of research, such as genomics and proteomics, will likely has-
ten the discovery of many more such products, as discussed below.

α (TNF- α

4.3 The impact of genomics and related technologies upon drug
discovery

The term 'genomics' refers to the systematic study of the entire genome of an organism. Its core aim
is to sequence the entire DNA complement of the cell and to map the genome arrangement physically
(assign exact positions in the genome to the various genes/non-coding regions). Prior to the 1990s,
the sequencing and study of a single gene represented a signifi cant task. However, improvements
in sequencing technologies and the development of more highly automated hardware systems now
render DNA sequencing considerably faster, cheaper and more accurate. Modern sequencing sys-
tems can sequence thousands of bases per hour. Such innovations underpin the 'high-throughput' se-
quencing necessary to evaluate an entire genome sequence within a reasonable time-frame. By early
2006 some 364 genome projects had been completed (297 bacterial, 26 Archaeal and 41 Eucaryal,
including the human genome) with in excess of 1000 genome sequencing projects ongoing.
From a drug discovery/development prospective, the signifi cance of genome data is that they
provide full sequence information of every protein the organism can produce. This should result in