From childhood, Spear had an interest in science and a curiosity about nature, instilled in him from his father. As an undergraduate, he was attracted to the fields of ecology and developmental biology, but eventually chose the latter because of the intellectual appeal of the genetic questions that it raises, and perhaps a premonition that genetics would be a driving force in the advancement of science and technology. Along the way, he has studied protozoa, bacteria, mice, even the biological control of pests. But during his 24 years at Abbott, his scientific quest has placed him squarely at the center of one of the most important advances in modern medicine - unraveling the secrets of human genetics to better understand disease and individualize and optimize medical care.

One of the applications of human genetics that Spear is leading at Abbott is aimed at improving the efficiency of the research and development process. The field of toxicogenomics uses the measurement of gene expression to get an early read as to whether a particular drug candidate may be causing adverse effects. Scientists can compare the way a new drug affects gene expression with an existing drug and get an idea if the new one will behave like the old one. If troublesome compounds can be detected early on, then research on them can be halted well before they reach later, more expensive stages of development. "We're working on methods now where we will be exposing cells in culture, tiny little dishes of cells with small amounts of compounds and be able to predict very early if there are toxicities that could occur in a normal [drug development] process two or three years later." The result: more effective and less costly drug development that lets the company focus on the potential winners. Spear has been a strong advocate for this approach: "Here at Abbott I think we're using [toxicogenomics] particularly aggressively as part of our regular drug development. there are few compounds now that come through the process that haven't been screened by toxicogenomics."

Spear has found that pharmacogenomics (the relationship between drug response and individual genetics) can be used to improve later stages of drug development as well. One of the many difficulties that researchers must contend with is the variability in response among patients. Some patients respond as anticipated, while others may be off the charts. "If we can explain that genetically, and often we can," says Spear, "it lets us understand better how our patients are likely to respond," and that information can be used to either shelve the drug or continue researching it.

Spear has seen a lot of change over the course of his career. How big an impact does he think pharmacogenomics is having on research? "I'd say that right now it's changing the way we're thinking about drug development but it's still early. By and large we don't see the consequences of pharmacogenomics being shown in the drugs coming out of development. But here and at many other companies now, acquiring genetic information on subjects is a normal part of carrying out clinical trials."

"Our job in pharmaceutical research is to come up with new drugs that are going to be effective and safe for as many people as possible. but the normal way of doing things is getting harder and harder. It's more expensive and there are many failures.We have to do this better and we can do it better.Using a more personalized approach, we can identify the people for whom [a drug] will be most effective and safe, or the doses at which it will be most effective and safe."

This article is based on a personal interview with Dr. Spear and on citations from the following:

Spear BB, Heath-Chiozzi M, Huff J. Clinical application of pharmacogenetics.
Trends Mol Med. 2001;7(5):201-4.