Systems Biology is a system's level approach to provide a complete understanding of complex biological systems beyond the molecular-level scale. It is the study of an organism, viewed as an integrated and interacting network of genes, proteins and biochemical reactions which give rise to life. Instead of analyzing individual components or aspects of the organism (called reductionist approach), such as sugar metabolism or a cell nucleus, systems biologists focus on all the components and the interactions among them, all as part of one system. These interactions are ultimately responsible for an organism´s form and functions. Understanding at system-level means that we can reproduce a system/phenomena on computer simulation, control its behaviour in a predictive fashion, and design such systems.

Most of us are so accustomed to the word "system" used in our everyday dialog, we rarely think about what it means. A formal definition might note that a system is a group of parts that come together, interacting and interdependent, to form a more complex whole unit. A simpler and more familiar way to say this might be that the whole unit is greater than the sum of the parts. Before we look into the broad implications of this idea, and how it relates to "systems biology", let's look at a very simple system.

Consider for a moment the following three items:

1. A small metal cup, about the size of a walnut.

2. A glass bowl, in the shape of a small balloon.

3. A length of tungsten wire, very brittle alas, pinched up into a small coil.

On their own, each of these parts is rather useless. But what happens if we put them all together? The wire coil could be tucked up inside the glass balloon; the metal cup could be attached to end of the glass balloon, sealing off the opening. This would allow us to create a vacuum inside the glass balloon. The metal cup could also act as electrical contacts, passing current to the wire coil. Suddenly we have three relatively useless parts working together as a system: An Electric Bulb. This electric bulb although useful as stand alone, it is often a part of more complex systems like appliances, automobiles, even stadiums.

Similarly, systems are comprised of parts which interact. The interaction of these parts gives rise to new properties and functions which are a key to the system. We call these new properties and functions "emergent properties". Because emergent properties are the result of interactions between the parts, they cannot be attributed to any single parts of the system. This makes systems irreducible. A system is unlikely to be fully understood by taking it apart and studying each part on its own. To understand systems, and to be able to fully understand a system's emergent properties, systems need be studied as a whole. This recognition that complex systems, especially life, are truly understood from knowledge of the interactions of their component parts is fundamental to systems biology.


Systems biology emerged as a result of the genetics "catalogue" provided by the Human Genome project, and a growing understanding of how genes and their resulting proteins give rise to biological form and function. Biologists can now "read" the source code of any species whose DNA they can isolate. The genes, and the proteins they encode, constitute a "parts list" for any said species. Once the parts are in hand, a focused, yet global, investigation of how their molecular interactions engender the distinctive properties of the species becomes more tractable and more exciting. Current studies in Systems Biology are being applied to numerous areas, including the so called complex diseases.

Systems Biology involves bringing together a multidisciplinary group of scholars and scientists, from biologists, mathematicians and engineers, to computer scientists and physicists, in an interactive and collaborative environment. There has been a vast increase since year 2000 in the number of publications, news articles, web pages, journals, and academic organizations devoted to systems biology. Clearly, this integrative approach has captured the imagination of biologists and the wider scientific culture. Methodologies for performing systems biology research are being developed and becoming more standardized. Nonetheless, the field still faces significant experimental, technical, computational and sociological challenges that will need to be addressed over the next several years. The complexity of humankind´s genetic makeup (approximately 25,000 genes) plus the myriad of proteins produced from these genes, give rise to the extraordinary functions of human beings (emergent properties), and the corresponding complexity of a human being as systems. Thus, understanding complex systems like human beings is only a dream at present.

The principles borne in mind by Systems biologists are:

1. Global approaches should be taken to data collection and analyses.

2. Information derived from diverse data types should be integrated.

3. Mathematical and statistical modelling is essential to the quantitative analysis of a system's properties.

4. Biology should drive technology which, in turn, makes better biology possible.

5. Systems biology research should create an interactive inter-disciplinary scientific culture.

6. The results of research should be freely disseminated.


The traditional approach to studying biology and human health has left us with a limited understanding of how the human body operates, and how we can best predict, prevent, or remedy potential health problems. Biologists, geneticists, and doctors have had limited success in curing complex diseases such as cancer, HIV, and diabetes because traditional biology generally looks at only a few aspects of an organism at a time.

Perhaps the most excitement about systems biology lies in the area of predictive, preventive, personalized and participatory (P4 Medicine TM) medicine: Predictive, Preventive, Personalized, and Participatory

Prediction: The technologies and tools of systems biology will provide medical practitioners with two exciting sources of health-related diagnostic data: By examining an individual´s complete genetic makeup, a physician will be able to generate comprehensive predictions about the patient´s health prospects. And by examining protein markers which naturally occur in an individual´s blood, a physician will be able to accurately determine a person's health status, including both the current effects of any abnormal genes and the current reactions to any environmental toxins or infectious pathogens. The goal is to identify pathogenic changes in cellular networks at the earliest possible stage and, with appropriate therapy, prevent or limit the deleterious effects of a disease.

Prevention: The new approach to medicine, based on each individual's genetic makeup, will help us determine the probability of an individual contracting certain diseases, as well as reveal how an individual may respond to various treatments, thereby providing guidance for developing customized therapeutic drugs. Thus another use of the technologies and tools of systems biology will be to develop preventive treatments for individuals, based on their potential health problems, as indicated by their genetic makeup and current blood-protein markers.

Personalized: On an average, each human differs from another by less than one percent of their genetic makeup. But these genetic differences give rise to our physical differences, including our potential predisposition to various diseases. So the ability to examine each individual's unique genetic makeup and thereby customize our approaches to medical treatment is at the heart of systems biology.

Participatory: As a result of personalization, patients will actively participate in personal choices about illness and well-being. Participatory medicine will require the development of powerful new approaches for securely handling enormous amounts of personal information and for educating both patients and their physicians.

Systems biology promises to transform how biology is done. Cutting edge biology drives the invention and development of new technologies that, in turn, expand the scope of what biologists are able to discover. It is anticipated that systems biology will continue to spur technology development in new and, quite possibly, unanticipated ways. For example:

1. The need to process minute quantities of large numbers of samples on which thousands of measurements can be made simultaneously is motivating the invention of nanotechnology and micro-fluidic devices.

2. DNA sequencing is another area in which technological advances are likely. The National Human Genome Research Institute has requested proposals for developing high-throughput, inexpensive technologies for sequencing entitled "revolutionary genome sequencing technologies -- the $1000 genome".

3. The problems of systems biology are seen as exciting to mathematicians and network theorists, so there are grounds for optimism that the required computational breakthroughs will be forthcoming.

4. With a catalogue of, say, gene regulatory network modules in hand, genetically modified bacteria might be engineered to facilitate environmental clean-up of toxic wastes or increase carbon sequestration from carbon dioxide (i.e., reducing the "greenhouse" effect) or produce alternative sources of energy to replace coal and oil which will become scarce, over the coming century.

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