The ID Report

By Robert Deyes

In an article that appeared in 2003, one of the stalwarts of modern chemistry Emeritus Professor Theodore Brown (Ref 1) provided an elucidating description of the cell in what was an article focused primarily on the use of metaphors in science. For the cell, the metaphor that Brown proposed was of a factory with complex functional relationships and interactions closely reminiscent of that seen in our own manmade production plants (Ref 1). Indeed today we know that the cell shows elements of quality control, energy budgeting, transportation of goods and services, review of process efficiencies and all the wonderful synchronies that one associates with a production line. Science writer Peter Forbes had this to say about the cellular world that until comparatively recently was a 'Blind Zone'- a black box unknown to man

"What exists in the Blind Zone are large molecules of complex non-random chemical composition that are assembled to make the working structures of the cell; pumps and engines and factories for making everything the cells need, including copies of themselves. The contents of the Blind Zone comprise nature's nanotechnology" (Ref 2, p.10)

Francis Crick's own reference to the cell's molecular 'gadgetry' also reflected the sophistication of the cellular world (Ref 3). Nancy Pearcey and Charles Thaxton likened the cell to an enormous factory, noting that if a cell were magnified many times over we would observe, "robot-like machines- tens of thousands of different kinds- in charge of production.....analogues to nearly every feature of our own advanced machines" (Ref 4, p.221). As biochemist Bruce Alberts has made all too clear, contemporary biochemistry has revealed a cellular world so replete with interacting, molecular machines that it most closely resembles a factory with numerous assembly lines each serving different functions in a bigger scheme (Ref 5).

In a landmark paper Marc Vidal and colleagues from the Dana-Farber Cancer Institute and Harvard Medical School took the factory analogy yet further by demonstrating how groups of proteins called 'hubs' are essential for establishing protein networks within the cell in what is now known as the protein 'interactome'. Proteins that make up the interactome interact closely with each other (Ref 6). Rather like big international airports that interconnect with other smaller national airports, hubs can be thought of as the backbone of the cellular communication and transportation network. Because of their importance the removal of these hub proteins would have disastrous consequences for the cell. It turns out that the cell has two kinds of hub protein- the 'party' hubs that interact with many proteins simultaneously and the 'date' hubs that interact with many proteins but only at different times and at different locations within the cell (Ref 6).

The identification of such organized modularity provides no basis for supposing that complex systems such as the cell could simply come into existence without any guidance or design. Proteins have specific enzymatic properties that invariably require them to be at specific locations within the interactome. To appreciate the magnitude of the vast number of interactions involved we need only consider that the simple worm C.elegans has an interactome map containing approximately 3,000 proteins linked by nearly 5,000 potential interactions(Ref 7). Indeed one review compared the interactome to the engine in a car

"At first the jumble of boxes, wires, circuitry and hoses that meets your eyes more likely will confuse than inform. Careful examination, however, exposes an intricate order, in which modular processes interact with each other to build ever-larger systems culminating in a working automobile. A cell presents an equally confusing array of parts. But like the car, the cell can be analyzed as a series of interacting systems working together to build a whole greater than its parts" (see Ref 8)

The enzymes that make up much of the interactome are critical for cellular reactions if they are to occur at anywhere near the speed that is required by the cell (Ref 9, p. 1). Enzyme complexes like the proteasome- the cell's own garbage disposal unit (Ref 10, 11, 12)- and the chaperonins that fold cellular proteins into the right conformation (Ref 13) tell of a world chock-full of machines and motors that not only resemble but in some cases exceed the products of human invention. Reminiscent of Jonathan Swift's recounting of Lilliput in Gulliver's Travels (Ref 14), our knowledge of cell biology and biochemistry has opened up a realm of very small, interacting machines that give every indication of having been designed.

References
1. Theodore Brown (2003), The Art of the Scientific Metaphor, The Scientist, Volume 17, issue 21 p.10

2. Peter Forbes (2005), The Gecko's Foot: Bioinspiration- Engineering New Materials From Nature, W.W Norton, New York

3. Crick's reference to the 'gadgetry' of the cell appeared in Episode 1 of the DNA Series aired by PBS, Episode 1: "The Secret Of Life" see: http://www.pbs.org/wnet/dna/episode1/index.html

4. Nancy R. Pearcey and Charles B. Thaxton (1994), The Soul of Science, Christian Faith and Natural Philosophy, Crossway Books, Wheaton Illinois

5.Bruce Alberts (1998), The Cell as a Collection of Protein Machines: Preparing the Next Generation of Molecular Biologists, Cell Volume 92 pp.291-294

6. Jing-Dong J. Han, Nicolas Bertin, Tong Hao, Debra S. Goldberg, Gabriel F. Berriz, Lan V. Zhang, Denis Dupuy, Albertha J. M. Walhout, Michael E. Cusick, Frederick P. Roth, Marc Vidal (2004), Evidence for dynamically organized modularity in the yeast protein–protein interaction network, Nature 430, pp.88-93

7. "Mapping the C.elegans Interactome", Poster appeared in The Scientist, Volume 18, Number 12, June 21st, 2004

8. Jeffrey M. Perkel (2004) Validating the Interactome, The Scientist, Volume 18 (12) pp.19-22

9. Thomas Creighton (1993), Proteins, Structure and Molecular Properties, W.H. Freeman and Company, New York

10. Michael Groll, Lara Ditzel, Jan Lowe, Daniel Stock, Matthias Bochtler, Hans D. Bartunik, Robert Huber (1997), Structure of 20S proteosome from yeast at 2.4A resolution, Nature Vol 386 pp.463-471

11. Sherwin Wilk (2003), "The Search For Neuropeptidases And The Discovery Of The Proteasome". Seminar held at Promega Corporation, Madison WI on the 19th of November, 2003

12. Kenneth Chang (2004), Study of Cell Breakdown Captures Nobel, New York Times, October 7, 2004

13. Tatsuro Shimamura, Ayumi Koike-Takeshita, Ken Yokoyama, Ryoji Masui, Noriyuki Murai, Masasuke Yoshida, Hideke Taguchi, So Iwata (2004), Crystal Structure of the Native Chaperonin Complex from Thermus thermophilus Revealed Unexpected Asymmetry at the cis-Cavity, Structure Vol 12 pp.1471-1480

14. An electronic copy of Jonathan Swift's 'Gulliver's Travels', based on the original 1726 Motte edition, can be found at http://www.jaffebros.com/lee/gulliver/bk1/chap1-1.html