Caltech president David Baltimore (left) and Professor of Chemistry Robert Grubbs celebrate the news that Grubbs has been awarded the 2005 Nobel Prize.

Polymer Chemist Bonds with Nobel Prize

by Rhonda Hillbery

Back in the 1960s when he was a graduate student, Robert Grubbs became intrigued by a then little-understood chemical reaction. “When I started, it was a fundamental question: ‘How does this thing possibly happen?’” Speaking like a true research chemist, he adds, “There was no thought then of applications or anything else.”

He couldn’t foresee that his area of study—metathesis—would transform the field of polymer chemistry and prove to have applications ranging from the prosaic to the profound. It’s helped create new drugs, less toxic production processes, and environmentally friendlier pest control. And on October 5, it won Grubbs the Nobel Prize in chemistry. He and his two cowinners were cited specifically “for the development of the metathesis method in organic synthesis.”

Organic synthesis involves manipulating the molecular compounds that give rise to life—in other words, those that contain carbon. Metathesis is a reaction in which chemists selectively strip out certain atoms from one carbon compound and swap them with atoms from another compound. The end result is a custom-built molecule that has specialized properties.

Grubbs, 63, has worked in a branch of this field called olefin metathesis—metathesis that involves hydrocarbons, such as ethylene, that contain double bonds. Before he began his research into “how this thing could possibly happen,” metathesis was poorly understood and of limited value to scientists. Grubbs’s key contribution was to develop a powerful new catalyst for metathesis—“magic dust,” he colloquially calls it—that made it possible to create tailor-made molecules.

The Nobel citation says that use of the catalyst and its variations have improved industrial and pharmaceutical production processes, making them more efficient and less wasteful, as well as simpler and more environmentally friendly. “This represents a great step forward for ‘green chemistry,’ reducing potentially hazardous waste through smarter productions,” the Royal Swedish Academy of Sciences announced. “Metathesis is an example of how important basic science has been applied for the benefit of man, society, and the environment.” As for his catalyst that started it all, Grubbs says, “There are now about 15 variations of the basic structure.”

The lanky professor insists that he was surprised by the Nobel, although he admits that “people whisper in your ear.” He was spending a month as an Erskine Fellow at the University of Canterbury, in Christchurch, New Zealand, when he received the call from Stockholm at about 10:30 p.m., after a long day of traveling. He and his wife, Helen, were sitting around the fire “keeping warm and finishing a late dinner” when the phone rang. Over the next few hours, the new laureate celebrated with a bottle of port while he fielded a succession of media calls from around the world. Finally, he unplugged the phone and went to bed.

Actually, the laureate wasn’t the first in the family to learn the news. That honor went to son Brendan, who has just started an ob-gyn residency at USC Medical School and is temporarily living at his parents’ home. “While he’s settling in, he’s staying in his old place at home,” says Grubbs. “So he got to answer the phone call from Sweden, and passed along the phone numbers of how to reach us.”

After Grubbs heard from Sweden, his first calls were to his other children. Son Robert B. (Barney) is a polymer chemist and professor at Dartmouth, and daughter Kathleen is a graduate student studying clinical psychology at the University of Hawaii.

Although his stay in New Zealand was scheduled to last another week, Grubbs cut it short to return to the Institute, where colleagues, students, and postdocs were already celebrating. “I taught my classes there on Thursday and Friday and went for a walk on Saturday and then flew home on Sunday.” On Monday, the chemistry division and hundreds of well-wishers threw him a party in the Iris Garden, next to Crellin Lab, where he has carried out most of his work. The next day Grubbs was back to the business of being a Caltech scientist and professor.

The term metathesis literally means “change places,” and Grubbs credits the Swedish Academy for coming up with an analogy that compares metathesis to dance couples swapping partners. “My colleagues and I just came up with the molecules. We didn’t think about ways of explaining it.”

Caltech licenses the Grubbs metathesis technology through Materia Inc., an Institute spin-off that Grubbs founded in 1997 (he’s now the company’s scientific advisor). In his Crellin office, the mild-mannered scientist brandishes a baseball bat as he explains one technology application.

“This is made from a piece of wood that’s not very good, and there’s a shortage of really good wood for making baseball bats.” By inserting a polymer into the tiny spaces between the wood fibers, “the polymer strengthens the wood so now you can hit the ball 400 or 500 times without the bat breaking. Without the treatment, maybe it would break the first time you hit with it.” The bat is certified for use through Class A in baseball’s minor leagues, he adds.

Materia also sells its technology to agribusiness firms such as Cargill, which convert bioseed oils from crops such as corn and soybeans into industrial chemicals, livestock feed, and consumer products. Several companies use metathesis to produce insect pheromones to control a pest in peach production, reducing or eliminating the need for toxic pesticides. It works by interfering with the male peach twig borer’s sense of smell. “The concentrations they use are so small, it takes only a few grams to cover an acre,” says Grubbs. “Since it’s everywhere, the males can’t find the females, so there’s no mating and no destruction of fruit stock. Instead of spreading kilograms of pesticides everywhere and killing everything, you can use a few grams of this material.”

Meanwhile, the materials industry uses metathesis to produce pipes that are resistant to caustic corrosives. And pharmaceutical companies are utilizing it to develop drugs—not yet on the market—that treat osteoporosis and hepatitis C. “This process enables the drugs to be made much more quickly, and in some cases, it’s the only way to make them,” says Grubbs. “I think the excitement about it has to do with the fact that you go all the way from making stuff like this baseball bat to making pharmaceuticals, based on this one platform technology that is the catalyst.”

Helping make it all possible, he says, are the 22 grad students and postdocs who work in his synthetic chemistry group. “Graduate students work in the lab, make observations, and make many of the decisions that move projects forward,” he says.

An accomplished outdoorsman, Grubbs, shown here at Eaton Canyon, enjoys rock and mountain climbing.

In the Nobel citation, Grubbs and his fellow laureates were credited with each providing a piece of the metathesis puzzle. Yves Chauvin, now retired from the French Petroleum Institute, explained in the early 1970s how the reaction worked, and provided the “recipe.” Richard Schrock, a chemistry professor at MIT, is credited with being first to produce an efficient metal-compound metathesis catalyst in 1992.

“I’ve been a good friend and competitor with Dick for years,” Grubbs says. He recalls that his own biggest breakthrough came in 1992, when he developed the first in a series of improved catalysts that became commercially viable in 1994. Produced with ruthenium, it is stable in air, can be used in alcohols and water, and is more selective in directing reactions.

Grubbs maintains that he did not originally foresee green chemistry growing out of his basic research, but calls that outcome a welcome benefit. “There are some cases where an industrial process would take seven or eight steps, with lots of solvents. Using this catalyst, you compress it down to one step with no solvents. In terms of waste and processing, it’s a good savings.”

Grubbs grew up in Kentucky, where he did plenty of the same square dancing moves that the Nobel committee used as an analogy for the chemical reactions in metathesis. After earning his BS and MS degrees at the University of Florida and his PhD in chemistry at Columbia, he spent a year at Stanford as a postdoc and nine years on the faculty of Michigan State University before joining Caltech as a professor in 1978. Elected to the National Academy of Sciences in 1989, he was named the Atkins Professor of Chemistry in 1990.

Grubbs’s Nobel Prize brings to 32 the number of Nobels won by faculty and alumni. The new laureate says he is looking forward to traveling to Stockholm in December with his family to receive the medal.

“I just got the travel plans for the Nobel celebration and it sounds like a pretty wild week. Apparently there are great parties. It will be great fun to go to them with my kids.”