WE are in the midst of revolution in the biological sciences. While the 20th century has been termed the century of physics, heavily dominated by the advent and rise of computers and telecommunications, the 21st century may well be the century of biology and medicine. The foundation for this change is the science of genomics, which began in the mid-1980s and was accelerated by the huge success of the Human Genome Project.|
At that time, some claimed that sequencing the human genome was a dream-that biotechnologies to support such an effort did not exist or were not sufficiently advanced. Times have changed, and the technologies are available. The pace of the human genome effort is accelerating. The original plan was to complete the sequence of the human genome by 2005. In the last year, that target completion date first changed to 2003 and is now 2001. Moreover, other species are beginning to be sequenced, including the mouse, plants, and microbes. Knowledge of these other species provides insight into human disease, crop improvement, bioremediation, and pathogen diagnostics.
The Human Genome Project primed the pump for this bioscience revolution. Today, bioscientists' visions are not focused on whether they can sequence the genome, but how fast they can do it, and how we as a species can capitalize on the information for the diagnosis, prevention, and treatment of disease. In other terms, we need to functionalize the sequence data. The successes of the genome project have generated a set of new bioscience visions with semantic descriptors such as functional genomics, proteomics, and structural genomics.
It must be remembered that the DNA sequence being determined is really a code. The code is read by complex molecular machinery in the cells of our body. The products of genes that are encoded in the DNA sequence are proteins. Proteins, themselves, are the engines of our body. They are responsible for our body's metabolism; they play a role in structure at the cellular, tissue, organ, and whole-body level; and they can protect us from, or even cause, some diseases. Understanding how proteins function is essential to understanding how biological systems work. Protein function can be investigated several ways-by biochemical methods, genetic approaches, or structural and computational analysis. All approaches are complementary and generally necessary to characterize the biological function of a single protein.
The article entitled Structural Biology Looks at the Ties That Bind describes one of Livermore's approaches to and accomplishments in protein structure analysis, that is, using crystallographic and diffractometry techniques to determine the three-dimensional structure of proteins at the atomic level. Once a three-dimensional structure is determined, computational methods can be used to model function and potentially to design drugs or inhibitors that interact with the protein to either enhance or modify its function. The Department of Energy and its national laboratories are bringing unique, multidisciplinary physical, engineering, and computational resources to bear on these efforts.
While the world is still dealing with unraveling the structure and function of proteins one at a time, each of which might take years of research, it is clear that this one-by-one approach is not sufficient to deal with the expected 100,000 or so proteins in the human genome. The challenge to the scientists is to find ways to multiplex protein functional analysis, just as DNA sequencing has been multiplexed. Then myriad proteins can be researched in parallel. So the answer to the question "Is there life after the human genome project?" is not only yes, but a resounding yes.