Drug data for a custom fit.

When it comes to drugs, one size definitely does not fit all. Now a new resource may help researchers individualize medicine. The Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB) is one way that researchers are working toward individualized medicine. PharmGKB is the face of the Pharmacogenetic Research Network, a collaborative group of scientists who study the effect of genes on people's responses to a wide variety of medicines. The network was launched by the National Institute of General Medical Sciences three years ago and now includes members at five other NIH branches and eight universities.

"Pharmacogenetics is all about variation," says Mayo Foundation pharmacologist Richard M. Weinshilboum. "Our goal is to help predict which patients will have an adverse response to a drug and which patients need higher or lower doses," he says. "This will lead to true individualization of therapy."

Although some researchers use "pharmacogenetics" and "pharmacogenomics" interchangeably, others distinguish pharmacogenetics as the study of how one person responds to a drug, and pharmacogenomics as the use of genomic information to guide new drug development.

PharmGKB is accessible via a free, publicly available website located at http://www. pharmGKB.org/. It contains genomic and phenotypic data, and links them all together. The data complement the genome database by offering gene variants and linking these variants to abnormal responses to drugs. Researchers can both search the database and add their own findings.

One of the most exciting submissions to date, says Russ B. Altman, a Stanford associate professor of genetics and medicine who is the principal investigator in charge of the database, is a compilation of two dozen variations in transporter genes involved in the metabolism of medicines, submitted by a team at the University of California, San Francisco (UCSF). Some of these variants are responsible for differences in transporters that pump environmental toxicants out of intestinal tissue before they can be absorbed. This protects the body against harmful chemicals, but can also produce unintended drug responses, says principal investigator Kathleen M. Giacomini, chair of the UCSF Department of Biopharmaceutical Sciences. For example, super-effective transporters can pump out drugs before they are therapeutically absorbed, whereas nonfunctional transporters offer no defense against environmental insults and may make a person hypersensitive to medicine.

"It's pretty new and exciting for the NIH to run this cross-institutional project," says Harvard Medical School researcher Scott Weiss, who is zeroing in on a handful of genes that affect an asthma patient's response to inhaled steroids. Researchers within the network who study heart and lung function are now focused on similar genes and are sharing their results, Weiss says. "It has taken us quite a while to get moving, but I think this year will be a big one for the network as a whole."