Exploring "Molecules That Changed the World"

By Mika Ono

Have you ever wondered what impact modern chemistry has had on our lives? K.C. Nicolaou, chair of the Department of Chemistry at Scripps Research, explores the many answers in his fascinating new book Molecules That Changed the World (Wiley-VCH, 2008). Co-authored with Tamsyn Montagnon, a former postdoctoral fellow in his lab who is now conducting research at the University of Crete, the book lays out a series of stories of molecules—from penicillin to vitamin B12—that altered the course of human history.

"In this book you'll find history, personalities, Nobel Prize winners," Nicolaou said at a recent event hosted by the California Office of Philanthropy for donors and friends of Scripps Research. "You'll find chemistry, biology, and medicine—and most importantly, you will learn of the enormous impact of the sciences on society."

Take Aspirin® (acetylsalicylic acid), which Nicolaou calls "the most successful medicine of all time." More than 3,500 years ago, Egyptian physicians recommended an herbal preparation made of myrtle bark for the treatment of rheumatism and back pain. One thousand years later, Greek physician Hippocrates advocated chewing on the bark of the willow tree to ease the pain of childbirth, as well as to treat other types of pain and to reduce fever.

Thanks to the efforts of scientists over the last 250 years—including Edward Stone, Johann Andreas Buchner, Raffaele Piria, Charles Frédéric Gerhardt, Karl-Johann Kraut, Hermann Kolbe, and Felix Hoffmann—the active ingredient of the bark (salicylic acid) was identified, purified, and chemically manipulated into the medicine we know today, which was registered as Aspirin® by the company Bayer in 1899.

Nicolaou points out that the story of this amazing molecule doesn't stop there. The study of its mechanism of action has increased our understanding of pain and inflammation, and led to the development of new drugs, including Celebrex®, which is prescribed for osteoarthritis, rheumatoid arthritis, and acute pain. Research has led to other applications for Aspirin® itself as well, such as its long-term use in low doses to reduce the risk of heart attacks, strokes, and blood clots.

Broad Appeal

Molecules That Changed the World straddles the niche between coffee table book—complete with gorgeous color pictures—and textbook, accessible enough to be read by interested high school students, but detailed enough to have much to offer more advanced readers.

"The book was written with the intention of inspiring young people into the sciences," said Nicolaou, "and also with the aim of informing the public."

The broad appeal of the book is reflected in its three prefaces, provided by high school student Anatolia M. Evarkiou-Kaku, who attends the Francis Parker School in San Diego; 1990 Nobel laureate E.J. Corey, a professor at Harvard University; and 2001 Nobel laureate Ryoji Noyori, an investigator at RIKEN and Nagoya University.

In the parade of more than 30 important molecules covered in the book, we see the power of nature, which provides an incredible array of products that chemists can then work to understand and manipulate.

"Nature is one of our best allies," said Nicolaou.

Another theme that comes out in these many molecular stories is the importance of supply. The widespread use of these molecules depends not only on their discovery, but also on scientists' ingenuity in enabling their mass production.

Nicolaou himself played a key role in this regard for the anti-cancer drug Taxol®, which Nicolaou calls a "celebrity molecule." Taxol®, whose active compound was first isolated from the bark of the rare Pacific yew, demonstrated great promise as a cancer treatment, but its full impact was prevented by the problem that treating one patient required the destruction of more than three of these precious trees. Nicolaou was the first to publish a synthesis of the active ingredient, opening doors to its further development.

Proceeds Support Scholarships

Nicolaou, who is Darlene Shiley Professor of Chemistry and Aline W. and L.S. Skaggs Professor of Chemical Biology at The Skaggs Institute for Chemical Biology, is one of the most cited organic chemists of all time, as well as a committed teacher.

He has been honored with more than 50 awards, and is a fellow of the New York Academy of Sciences, fellow of the American Association of Arts and Sciences, member of the National Academy of Science, and corresponding member of the Academy of Athens, Greece. Nicolaou is the co-author of several other books, including Classics in Total Synthesis (with former student Erik J. Sorensen, now a professor at Princeton University) and Classics in Total Synthesis II (with former student Scott A. Snyder, now a professor at Columbia University).

Proceeds from the book support postdoctoral and graduate students at The Scripps Research Institute.

"It is the excitement of interacting with young people that keeps me going," Nicolaou said.

For more information on Nicolaou, see his lab's website at http://www.scripps.edu/chem/nicolaou/ .

For more information on Scripps Research Philanthropy Department events, which on September 3 also included an address by Eric Fallon, associate director of manufacturing sciences and technology at Genentech, and introductions by Phil Baran, a former student of Nicolaou's who is now also a professor at Scripps Research, see http://www.scripps.edu/philanthropy/labnotes.html

Send comments to: mikaono[at]scripps.edu

Renowned chemist K.C. Nicolaou signs a copy of his most recent book at an event for donors and friends of Scripps Research.