The Twelfth Link: The Map of Life

The following is an excerpt from an interview I conducted based on some of the ideas in Barabasi's book. My goal was to get a scientist's perspective on Barabasi's network approach to biology and DNA sequencing.

Introduction: Albert Barabasi is an author who wrote the book Linked: The New Science of Networks. As a course in the College of Creative Studies through the University of California Santa Barbara, we are using this book as a foundation for research and art projects. In his Chapter "The Map of Life" Barabasi emphasizes a network approach to biology, in particular DNA sequencing. I am going to ask you to answer a few questions in relation to his argument, as well as some questions pertaining to your job position.

1) First of all, what is your current job title?

Ron: I am a research associate, in molecular biology, at AMBIT biosciences corporation.

2) What are some of the types of projects you are currently undergoing?

Ron: Some of the projects that I am working on involve DNA sequencing, DNA analysis, bioinformatics, and the utilization of automated DNA sequencing equipment, and computers/robotics, for high-throughput sequencing itself.

3) What does your company seek to find through its research?

Ron: My company seeks to identify new peptides, and small molecules, which will lead to drugable proteins, or drug discovery. In short, we are discovering how specific drugs, which are already on the market, actually work, but identifying the underlying protein pathways which enable the drugs to produce their therapeutic effects. This, in turn, will lead to a greater understanding of protein interaction, or pathways, themselves, thereby enabling us to invent new drugs, or to improve already existing drugs, on the market.

4) Barabasi, writes that in 1987 Nature Magazine featured an article saying it found the gene for manic depression. It located the gene responsible as chromosome 11. Later reports refuted this discovery, and laid claim to other chromosomes responsible ie: 6, 13, 15, and 18. Barabasi writes that rather than being conflicting results, these discoveries demonstrate that most illnesses and not caused by a single malfunctioning gene. Rather, "several genes interacting through a complex network hidden within our cells are simultaneously responsible." This reasoning seems obvious now, but why do you think in the late 1980s scientist were primarily looking for defects in single chromosomes themselves?

Ron: Scientists were originally not aware of the fact that not one gene, but actually a system of genes, encode for particular traits, or characteristics; as they are developmentally regulated in their gene expression. Hence, although the human genome is now completed, scientists now are faced with the undaunting task of unraveling how, and which, genes work together, in developmentally regulating the expression, and systematic development, of proteins themselves. This has led to the explosion of the new field known as bioinformatics, and the subfield of proteomics, in which scientists, and biologists, are taking a much more computational approach to molecular biology, and genomic data/DNA itself.

5) On June 26, 2000, Bill Cllinton announced the decoding of the 3 billion letters of the human genome, saying we have been handed the "book of life." Barabasi writes," We are repeatedly told that everything from our personality to future medical history is encoded in this book. Can you read it? Let me share a secret with you: Neither can biologists or doctors." Barabasi agrees that the genome project is a triumph in reducing complex living systems to their smallest parts. But he stresses in order to really understand how illnesses work, we need to look at how the cell functions as a network. Do you agree with this statement?

Ron: Yes, as I just mentioned, cells function as a network, because they are instructed to do so by a network of genes themselves, which encode the function of the cells. In other words, the metaphor of a network of genes is exemplified within the functioning of the network of cells, where cells function as a by-product of the genetic networks instructing them.  

In short, in the world of molecular biology today, form determines function, whereby protein interactions, and developmental pathways, ultimately determine the function of a particular trait, or characteristic, which is ultimately determined by the underlying genetic pathways, or networks, themselves.

6) Similarly other scientists are studying diseases in terms of a network. In cancer, for example, scientists found that the p53 gene is responsible. But instead of obsessing over the p53 molecule, Barabasi writes that we should focus instead on the p53 network: a sum of all molecules interacting with the p53 molecule. Do you agree with this idea? How does this relate to your own research?

Ron: Yes, diseases are usually the result of defects in proteins, or particular sub-units, which interact with other molecules. Although these proteins are encoded for, or translated, through their DNA expression itself, other defects in protein folding are ultimately the result of diseases themsevles. My company is involved in researching, and discovering, the underlying protein pathways by which drugs, which are on the market, actually work, thorugh looking at different protein interactions, and pathways. In short, we use a phage-display approach to our patented gene technology, which thus enables us to measure protein-to-protein interaction, thorugh affinity binding assays, and then to clone and sequence such proteins.

7) Finally, Barabasi says that once we understand DNA in terms of a network, scientists will be able to deliver prescription medicines catered specifically to an individual's DNA. Moreover, in producting antibiotics, scientists will be able to develop drugs which can kill a particular strain of bacteria, rather than wiping out all the bacteria in the body (good and bad bacteria) as current medicines do. He also says that this can be accomplished within the next 20 years. Do you think this is probable?

Ron: Yes, this can be accomplished, because Recombinant DNA technology will enable us to target, and sequence, individual bacteria, and hence to invent Ab's which are specific to certain starnds of the bacterial genome itself.

8) Last question. Do you think any of Barabasi's statements relate to your research? If so how?

Ron: His statements certainly relate to my research, given that today biotechnology is implemented in terms of both sequencing, and managing, DNA, or genomic data. Then, one must actually look at the whole cascade of protein/gene interaction, in terms of networks, which thus enables one to form databases; whereby the true goal is to manage, and analyze, the information that is yielded ultimately through the DNA/human genome project itself. In short, as DNA is the genetic material of life, one must now try to understand, on a larger-scale issue, how various genes work in concert with one another, in order to produce stably inherited functional design, or trait-inherited characteristics, in general.