Growth factors: the journey continues

Growth Factors is approaching its 30th year of publication (in 2018) and during that period has been expertly guided by the commitment of its inaugural Editor-in-Chief Tony Burgess. When Tony penned his introduction to Growth Factors in 1988 (A. W. Burgess, Growth Factors: The Beginnings, Vol. 1;1-6, 1988) (Burgess, 1988) this area was at a formative, but exciting stage. In the 28 years since there has been unprecedented advances in the understanding of growth factors, their receptors and signaling machinery, and their application to human development and disease. It has also been a period of significant change in how scientific discoveries and data are published, including the number, quality, and role of these journals. Re-reading Tony’s article (and I would highly recommend to all that you do) highlights the key role of earlier biologists and biochemists in establishing the field. Their efforts to isolate and characterize these often elusive ‘‘activities’’ using cell-based assays spanned decades of painstaking work. This was then followed by the role of the biochemist/protein chemist to purify and concentrate the activity with the hope of gaining initial primary amino acid sequence data for further identification. At the onset of Growth Factors, a number of revolutions were about to impact biological sciences and transform the humble beginnings of this field. Around 1988, biology/biochemistry was preparing to fully embrace a number of important technologies. One being monoclonal antibodies (mAbs), a discovery that gained Kohler and Milstein the Nobel prize in 1982, was revolutionizing the characterization and understanding of growth factors and receptors in general (Kohler & Milstein, 1975). This technological advance allowed an almost unambiguous identification of particular protein chains through immunoprecipitation and the new approach of Western blotting, and provided a renewable handle for biochemists to purify proteins through affinity chromatography (Williams & Barclay, 1988). While antisera would take a backseat to mAbs for the next 30 years as investigative reagents, the role of mAbs in human therapy would take another decade to overcome the hurdles of clinical application to become powerful therapeutic agents in their own right (Scott et al., 2012). Around the same time, recombinant DNA technology was about to transform biology. The groundwork for this was developed in the 1970s. Fred Sanger and Alan Coulson described a rapid method for sequencing DNA using DNA polymerase (Sanger & Coulson, 1975; Sanger et al., 1977) and this was followed by a chemical sequencing method described by Allan Maxam and Walter Gilbert (Maxam & Gilbert, 1977). At a similar time-point, scientists led by Paul Berg, Stanley Cohen, and Herbert Boyer would devise ways to splice together different pieces of DNA using restriction enzymes, introduce genetic material from one organism into the genome of another, and then allow replication and expression of the protein. Despite significant resistance to the development of this technology due to concerns about cloning and mixing of DNA from different species (Grobstein, 1977), the benefits of gene technology were soon realized through the commercial production of recombinant protein growth factors such as human somatostatin and insulin in the late 1970s. Human insulin (Humulin) was the first biotechnology product to appear on the market, made by the then new biotechnology company Genentech, and was approved for use by the FDA in 1982. Gene technology was also taking a firm hold in research laboratories, and the so-called ‘‘Molecular Biologists’’ or ‘‘Gene Jockeys’’ were fast becoming the pivotal research personal, as individual genes were being sequenced, and new genes being discovered at an express rate due to homology with preexisting genes. The rapid growth in availability of primary amino acid sequence data from proteins purified by affinity chromatography with the aid of mAbs, or through new expression cloning approaches (Aruffo & Seed, 1987), was a key driver to this process. A good example of the rapid expansion of knowledge during this time comes directly from the area of growth factors and their receptors. Andrew Wilks used polymerase chain reaction (PCR), another exciting new technology at the time, to devise a method to amplify novel members of the receptor tyrosine kinase family through a system of degenerate oligonucleotide primers which would amplify sequences of related genes from mRNA extracted from specific tissue sources (e.g. colorectal cancer tissue). This approach Address after June 2016: Peter MacCallum Cancer Center, Victorian Comprehensive Cancer Center, 305 Grattan Street Melbourne, VIC 3000, Australia