Table of Contents

May 2000
Vol. 3, No. 4

FEATURES
40	High-throughput genomics Enal S. Razvi and Lev J. Leytes A complete understanding of the DNA code that underlies human physiology is a key to unlocking secrets to normal functioning and disease, offering the promise of creating better drugs faster. But simply knowing the sequence is not enough. Single nucleotide polymorphisms (SNPs) are binary elements of genetic variability in the human genome that function as signatures for different biological traits, such as susceptibility to disease. Screening techniques for associating SNPs with biological function offer a way to use genomic information in drug discovery.
45	Tapping traditional healers' treasures Julian Josephson Biodiversity, particularly the diversity of plants, is the cornerstone on which nature's medicine closet is built. One approach to finding species with medicinal potential, a process referred to as "bioprospecting", is to take random samples of organisms and analyze them as potential sources of drugs or chemicals that can be made into drugs. The difficulty with this method is that it entails obtaining huge amounts of samples from far and wide and not having a clear point of departure from which to begin the requisite analyses. Although time-intensive, this method has been successful in the past and cannot be ruled out. Another approach that shows more promise is to prospect in parts of the world in which traditional or folk medicine is widely practiced. This type of medicine, which is practiced in places such as the Amazon rainforest, is still used to treat about 80% of the world's population.
52	Spot checks Alexander Kuklin Gene expression patterns can help illuminate pathophysiological processes and how they are affected by drug treatments. These patterns can be obtained in a high-throughput environment by using DNA array technology. A bottleneck in this technology, however, is management of the abundant information associated with microarray design, image processing, and data mining. Tools are available to help speed this part of discovery.
57	Barnyard biotech Mark S. Lesney Dolly, the clonal sheep, hit the newspaper stands and TV screens in 1997. This hapless ewe raised a media frenzy about the specter of human cloning. In point of fact, the media was correct. Dolly was indeed the template for the next wave of human cloning-not copies of human beings, but copies of human genes. Because of Dolly and her ilk, the future of many pharmaceuticals is "animal pharming"—the production of mass quantities of generic drugs in transgenic clonal animals.
67	Drug discovery adopts factory model David Kniaz In a highly integrated process like drug discovery, a significant change in one part of the system-such as high-throughput screening-creates a ripple effect through all other areas. So when dramatic changes are happening everywhere, the ripples turn into waves of change that can unbalance the entire research enterprise. This article reviews the driving factors behind today's drug discovery enviroment, outlines the key logistical challenges created by these changes, and offers guidelines for the research asset management systems that will continue to grow with the drug discovery enterprise.