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President's Introduction

lerner/Photo Richard A. Lerner, M.D.

This past year was another year of extraordinary scientific productivity for members of The Skaggs Institute for Chemical Biology, punctuated by the awarding of the 2001 Nobel Prize in Chemistry to K. Barry Sharpless. Coming so closely on the heels of the tragedy of September 11, this prodigious accomplishment lifted the spirits of the entire organization as we came together in celebration of Barry's remarkable scientific career. Long recognized by the scientific community for his seminal contributions, he has also received considerable attention from the philanthropic community, most notably Sam and Aline Skaggs, whose contributions have enabled him to achieve numerous research breakthroughs.

Dr. Sharpless was awarded this year's prize in chemistry along with William S. Knowles, formerly of Monsanto, and Ryoji Noyori, of Nagoya University, for "the development of catalytic asymmetric synthesis." Awarded annually by the Royal Swedish Academy of Sciences, the prize recognizes individuals who, as stipulated in Alfred Nobel's will, "have conferred the greatest benefit on mankind."

Dr. Sharpless has contributed innovations to the development of broadly useful and commercially practical catalytic oxidation chemistry for the selective production of bioactive chiral molecules with the proper right- or left-handedness. Chirality, or handedness, is the structural characteristic of a molecule that makes it impossible to superimpose the molecule on its mirror image. Proteins, DNA, and carbohydrates are all chiral molecules; without the correct handedness, they will not function as the basic molecules of life. Many drugs also must be of correct chirality; indeed, in some instances, the molecules with the wrong chirality can be toxic.

Dr. Sharpless's methods allow the manufacture of safer and more effective antibiotics, anti-inflammatory drugs, heart medicines, and agricultural chemicals. In 1980, he reported a breakthrough in synthesizing chiral molecules: the highly enantioselective epoxidation of allylic alcohols catalyzed by a titanium complex. This method is now used routinely. More recently, he developed another useful method, the asymmetric dihyroxylation of alkenes catalyzed by an osmium complex. In fact, Sharpless asymmetric epoxidation, dihydroxylation, and aminohydroxylation methods have revolutionized organic chemistry by transforming asymmetric synthesis from nearly impossible to routine.

Other significant honors bestowed on Dr. Sharpless this past year include the Wolf Prize in Chemistry and the Benjamin Franklin Medal. Also, he was listed among the "Top 75 Contributors to the Chemical Enterprise" in the 75 years since the founding of Chemical & Engineering News.

The British newspaper The Guardian this year ranked The Scripps Research Institute as the most influential institution in the world in the physical sciences, which include chemistry and physics. The rankings were based on how many articles faculty members publish and how often those articles are cited by other publications. The data used in the study were provided by the Institute for Scientific Information (ISI), the Philadelphia-based company that runs the Science and Social Science Index.

In addition, three members of the Skaggs Institute, K.C. Nicolaou, K. Barry Sharpless, and Chi-Huey Wong, were included in ISI's list of the world's most cited authors, a list that consists of less than one half of one percent of all publishing researchers. According to ISI, the list identifies "individuals, departments, and laboratories that have made fundamental contributions to the advancement of science and technology in recent decades." Further, ISI considers the information "a statistically powerful resource for finding individual authors who have formed or changed the course of research in a subject."

Members of the Skaggs Institute accounted for many meritorious research accomplishments this past year. One achievement that deserves particular commendation, however, is that of Geoffrey Chang, the Skaggs Institute's newest member, who joined its faculty this past October. His elucidation of an x-ray crystal structure provides the first detailed glimpse of a membrane transporter protein. Highlighted on the cover of a recent issue of Science magazine, the structure could be useful for improving cancer therapy and fighting antibiotic-resistant bacteria.

Antibiotic-resistant bacteria are a major problem in public health in the United States and worldwide. One way that bacteria resist antibiotic drugs is by using membrane transporters, large proteins that sit in the cell membrane and move other molecules in and out. In human cells, an important role of these transporters is the removal of harmful toxins. Unfortunately, harmful bacteria use transporters to nullify antibiotics. And certain cancer cells do the same thing, expressing membrane transporters on their surfaces that undermine the potency of chemotherapeutic agents.

Solving the structure of the membrane transporter protein creates the opportunity for scientists to design a new class of drugs that patients would take in conjunction with antibiotics or chemotherapeutic agents to keep those medications in the cells and increase their efficacy.

Overall, members of the Skaggs Institute made extraordinary progress this past year. Their work affirms the mission of the Institute and adds significantly to the body of knowledge at the interface of biology and chemistry. We owe a deep debt of gratitude to the Skaggs family, and to The Skaggs Institute for Research, for their foresight, generosity, commitment, and acknowledgment of the direction of the research. It is a true partnership for which we are most grateful and one that we are certain will yield important results for the betterment of humankind now and well into the future.



Copyright © 2004 TSRI.