Thought-provoking Article on Systems Biology from Sydney Brenner
We cannot say it better about the importance of this article from Sydney Brenner, which matches the sentiment we expressed in “Is 1000 Genome Project an Example of Modern Day Alchemy?”.
Sequences and consequences
Sequencing the human genome was once likened to sending a man to the moon. The comparison turns out to be literally correct because sending a man to the moon is easy; its getting him back that is difficult and expensive. Today the human genome sequence is, so to speak, stranded on a metaphorical moon and it is our task to bring it back to Earth and give it the life it deserves. Everybody understood that getting the sequence would be really easy, only a question of 3M Scienceenough Money, Machines and Management. Interpreting the sequence to discover the functions of its coding and regulatory elements and understanding how these are integrated into the complex physiology of a human being was always seen as a difficult task, but since it is easier to go on collecting data the challenge has not really been seriously taken up. I am sure that there will be many readers who will deny this and claim that there already is a way of confronting this problem through a new branch of biological research called Systems Biology. This is precisely the main target of my article; I want to show that the claims of radical systems biology cannot, in reality, be met and that it will not be possible to generate unifying theories on that basis. There is a watered-down version of systems biology which, to my mind, does nothing more than give a new name to physiology, the study of function and the practice of which, in a modern experimental form, has been going on since at least the beginnings of the Royal Society in the seventeenth century.
His proposed solution -
The alternative approach to systems biology is to solve a set of forward problems. The whole may be greater than the sum of the parts studied in isolation but the very existence of biological organisms tells us that it cannot be greater than the sum of the parts and their interactions. Cellmap aims to define the parts and their interactions and provide wiring diagrams as models of the system which we can use to compute outputs that can be compared with observations. We note here that when we come to simulate such systems, computation is carried out in the machine language of the system since all of the objects in Cellmap are the molecular entities themselves and not some description of them.
with a good analogy -
We may compare Cellmap with how our understanding of a city would be embodied in an analogous CITYMAP. The white pages of the telephone directory are like the genome sequence. We trust it to be accurate and complete and although it lists the people who compose the city it tells us little about how it might work. The yellow pages are comparable to the annotated sequence; they tell us a little more about function. Thus, a list of plumbers allows us to deduce that there will be pipes somewhere in the city because plumbers plumb pipes. However, the essential feature of the city is grasped only when we realize that there are units called homes in which families live; that in the morning, the families disassemble and the components then travel and aggregate with components from other homes in units such as schools, shops, banks, factories and that these are the functional units of the city. CITYMAP would need to embed knowledge both of the structure of these units and the flows between them. It would also find that the city had compartments, the city centre being distinct from the residential areas and that cities could differ widely as a consequence of their locations and history.
