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R & D Magazine’s 42nd Scientist of the Year

Mon, 12/10/2007 - 4:15am
George Whitesides
A Passion for Discovery

Before genomics, before computer software, and long before computer-aided chromatographs, a typical day in the chemistry lab involved arduous work. What might take minutes today required weeks a few decades ago, a fact well-known to George M. Whitesides who learned the chemist’s trade as a teenager in his father’s lab, studying compounds for rope treatments and enhancements to concrete.

Whitesides, R&D Magazine’s 2007 Scientist of the Year and the Woodford L. and Ann A. Flowers University Professor at Harvard Univ., Cambridge, Mass., was never put off by this aspect of his father’s science. Experiment after experiment with catalysts and crystals taught him how, he says, to see the patterns and make the associations that sparked his desire to make scientific discovery his career.

“If you like the routine part of it, then you’re probably okay, because then the high points will be all the more pleasurable,” says Whitesides of his decision to forgo studies in English and physics in favor of chemistry.

In the years after he launched his Whitesides Research Group—at about the same time he began teaching at the Massachusetts Institute of Technology, Cambridge, Mass.—the 69-year-old University Professor has taken full advantage of the tools that technology has brought. Now, it could be said, a computer is crucial in capturing the scope of knowledge his lab has generated. In his nearly 45-year career, he has had more than 900 scientific papers to his credit and currently holds more than 50 patents. His research group accounts for nearly a quarter of the patents generated from Harvard. A lecturer who remains committed to classroom teaching, Whitesides is also a force in the marketplace, having been involved in the formation of more than a dozen successful companies that, among other innovations, have introduced crucial drug treatments.

One of the U.S.’s most influential and oft-cited chemists, Whitesides directs all of this activity from an unassuming 557-m2 laboratory in the historic Edward Mallinckrodt Chemistry and Chemical Biology building just north of old Harvard Yard. Whitesides has been a professor there for more than 25 years, arriving after a 20-year career at nearby MIT.

A passionate educator, Whitesides is widely known for encouraging students to fully learn the R&D process as it relates to the real world. More importantly, he encourages them—both his laboratory staff and his classroom pupils—to open their minds to the breadth of learning potential.

Dr. George M. Whitesides, Woodford L. and Ann A. Flowers University Professor
Department of Chemistry and Chemical Biology
Harvard University, Cambridge, Mass.
Education & Academic Appointments
• AB, Harvard Univ., Cambridge, Mass.
• PhD, Chemistry, California Institute of Technology, Pasadena, Calif.
• Professor, Massachusetts Institute of Technology, Cambridge, Mass., 1963 to 1982
• Mallinckrodt Professor of Chemistry, Department of Chemistry and Chemical Biology, Harvard Univ., 1982 to 2004
• Chairman, Department of Chemistry and Chemical Biology, Harvard Univ., 1986 to 1989
• Associate Dean of the Faculty of Arts and Sciences, Harvard Univ., 1989 to 1992

Professional Affiliations
• American Academy of Arts and Sciences
• National Academy of Sciences
• National Academy of Engineering
• American Philosophical Society
• Member, Royal Netherlands Academy of Arts and Sciences
• Fellow, Institute of Physics

• Fellow, American Association for the Advancement of Science• Foreign Fellow, Indian National Science Academy
• Honorary Fellow, Royal Society of Chemistry
• National Institute of Health
• Department of Defense
• Member and chair, International Scientific Advisory Board of the Genomics Research Center, Academia Sinica
• Scientific Advisory Committee, Scripps Research Institute
• Past positions: National Research Council, National Science Foundation, Advisory Committee for Lincoln Laboratory, MIT

Honors
• American Chemical Society Award in Pure Chemistry
• James Flack Norris Award
• Arthur C. Cope Award
• Defense Advanced Research Projects Agency Award for Significant Technical Achievement
• National Medal of Science
• Von Hippel Award
• Pittsburgh Analytical Chemistry Award
• Kyoto Prize
• Paracelsus Prize
• Ralph and Helen Oesper Award
• Jacob Heskel Gabbay Award in Biotechnology and Medicine
• 2004 Dickson Prize in Science
• Dan David Prize
• Emanuel Merck Lecture Prize
• Linus Pauling Medal Award
• Welch Award
• U.A.A. Dhirubhai Ambani Lifetime Achievement Award
• Priestley Medal

“The most interesting problems in science are chemical problems. Stewardship, drug design, the origin of life, climate change, supply of water—those are all chemical problems,” he says.

“George goes after some of the most interesting challenges in science. You start to think the possibilities are limitless. He triggers good ideas and amazing science,” says Carmichael Roberts, vice chairman of Nano-Terra, a nanotechnology materials R&D startup in Cambridge, Mass., that was launched on the strength of new discoveries from the Whitesides Lab.

“Either from his lab or from his head, all kinds of ideas have been commercialized and companies started,” says H. Kent Bowen, a professor at the Harvard School of Business who has studied the Whitesides Lab and its model for successful R&D. “The overarching guide he uses is that it ought to be something that nobody else is doing or nobody else has done before.”

Whitesides is one of 21 University Professors at Harvard, and it is a “semi-honorary” title, says Whitesides, which allows him to teach whatever subject he wishes. His current course is one that is open to any student, including those with no science background.

This general course affords Whitesides the opportunity to teach students who may never have met a scientist. By the same token, he believes chemists, physicists and biologists could benefit from more exposure to ethics, history, and literature. This viewpoint is in keeping with Harvard’s mission as a liberal arts university. The act of teaching reinforces Whitesides’ own knowledge.

“I can’t imagine anything that has helped me more with understanding basic research than explaining thermodynamics or quantum mechanics or fluidics or gene regulation. If you can explain it to somebody, there’s an off chance you understand it yourself,” says Whitesides.

The Whitesides Lab – An innovation machine

Among the very first innovations to spring from the then newly-organized Whitesides Research Group in 1964 was the invention of the organic copper compound, which is basically a methyl group attached to copper molecules.

“At the time it was not known that such compounds could exist. There were no examples of compounds that had single bonds between single-metal elements and carbon. It was thought they were too unstable to exist,” says Whitesides. His research was successful—not only were these compounds stable, they also proved to be useful in organic synthesis. The development took a leap of imagination—before this research, transition metal organometallic chemistry didn’t yet exist. Whitesides Research Group’s mission can be summed up succinctly with this philosophy from Whitesides: if people aren’t using your research for their own efforts, 10 years from now, you haven’t done your job.

The Whitesides Research Lab hallways are deceptively tight. More than 50 projects are simultaneously ongoing, some active, some not. Most students are interested in chemistry, of course, but the researchers are a mix of medical doctors, engineers, and physicists. They are chosen not to solve a specific problem, but to contribute their ability to the overall problem-solving power of the lab.

As Whitesides himself says, his lab operates quite differently than undergraduate school. What is taught here is the process of furthering discovery, from the glimmer of an idea to a viable solution in the commercial sphere.

As unorthodox as these methods may sound for Harvard, entrenched in academia as it is often perceived to be, an aggressive approach to original ideas is actually safer, says Whitesides. “Creative ideas get rewarded,” and constitutes credit when those ideas are validated, he says.

At the Whitesides Lab, Bowen says, “failures are not failures. You not only learn that (something you tried) didn’t work, you find a way through the maze. How did this process go on? The net result is creative research and output,” he says.

A successful project being researched now involves electrets—materials that have a permanent charge. Whitesides became interested in the subject when thinking about the charge released when feet shuffle across the carpet in wintertime. Soft lithography, on the other hand, drew interest in a purely technological sense. Whitesides recognized that problems were limiting the potential of this technology and set about resolving the cost structure and perceived size constraints. This is still part of the research group’s work. Drug design efforts, meanwhile, focus directly on public health.

An important characteristic of the group is that it operates more as a professional R&D venture than as a traditional thesis advisor-student dialectic. Whitesides compares himself to a CEO—“you have to be careful with that phrase,” he says—but it’s close to the truth. While he may not know how to run the electron microscope, he knows how to provide the money to make it available, and part of his role as “CEO” is to help the students learn to procure that grant money themselves. He is also responsible for quality control and for the accuracy of the results. He exercises control in strategic directions but tries to keep his lab’s staff in control of their own projects.

According to research from the Harvard School of Business, led by Bowen and lecturer and post-doctoral fellow Francesca Gino, patents originating from the lab have numbered at least four per year this decade, reaching a high of 11 in 2004. The number of publications was 29 that year, which marks a lower than usual output—more than 50 papers were published in 2002. Whitesides says 40 each year is average. Steady and productive research helps spur grant activity, too, which has steadily increased from $2 million a year early this decade to now more than $3 million yearly.

The Whitesides Lab is also a force outside the university. Bob Benson, director of business development at the Office of Technology Development at Harvard, is in a good position to witness the development of new technologies and subsequent introduction to the marketplace.

“[George] has been doing it for so long, he doesn’t use this office or me. In terms of patent filing, he is the most prolific in terms of intellectual property at Harvard Univ. His lab is responsible for more than 25% of the university as far as patent filing. There are a lot of prolific people here, but George [Whitesides], he’s a polymath. He knows much better than me his impact, and he’s having an effect,” says Benson.

Science and business meet

Among the distinguishing features of George Whitesides’ tenure at Harvard Univ. is the consistency with which he is able to not only stimulate lab research but also direct it out into the open. He co-founded biotechnology giant Genzyme in the early 1980s. GelTex emerged in 1993, which was later acquired by Genzyme.

The Chemical Laboratories represent the major part of Harvard’s Cabot Sciences Complex. The Whitesides Lab is on the second floor at far right.

“The story of GelTex is very well known,” says Roberts, a former Whitesides Lab graduate student and a long-time collaborator of Whitesides who has known him for nearly 20 years. At the heart of the company, he says, was a compound developed by Whitesides that treats people with kidney failure. Kidney failur requires dialysis, a side effect of which is the buildup of phosphates in the intestinal tract. The treatment has been to transform the phosphors to salt using calcium suppositories. This is very painful.

Whitesides’ innovation was Renagel, a drug that binds the harmful phosphates eliminating the harmful metallic accumulation.

“[GelTex] is currently being sold, and it’s maybe over $500 million in sales. This is more important than almost anything George has done. It’s really helped a lot of people and it’s something to be proud of,” says Roberts.

Whitesides helped found Theravance Inc. in 1996, which finds cures for infectious diseases, and more recently has launched Surface Logix, Nano-Terra, and WMR Biomedical. All told, his efforts have helped start more than a dozen companies with a combined market capitalization of more than $20 billion.

In June of this year, more than 50 issued and pending patents regarding nanoscale and microscale molecular fabrication methods developed at Whitesides Lab were licensed to Nano-Terra under Roberts’ guidance. The company develops innovations such as flexible electronics, fuel cells, sensors, and smart materials and surfaces.

Roberts has taken Whitesides’ approach to heart. He says too often R&D facilities will generate new technologies and offer them up for grabs. Venture capital swoops in, attracted by the potential. Unfortunately, “when you have technology in search of a problem, and you have venture capital looking for immediate returns, you have a lot of pressure.”

“[Whitesides] is also very selective. He can raise millions just like that, but he realizes he has a responsibility to the company he is trying to create,” says Roberts. It’s no secret that most ventures fail, even those based on solid, high technology. In part what explains why Whitesides is such a magnet and filter for new scientific ventures is that his companies very rarely fail.“The major thing is that starting a company is something that involves a lot of different skills.

Everybody has to work together,” says Whitesides. “If you have a good idea, but don’t have good management, then you don’t have a good company.”

Guaranteeing a future for science

Whitesides’ impact on R&D creates a shockwave that ripples far outside Harvard. Genetics, nanotechnology, and medical instrument supply companies that represent billions of dollars of market capital owe their existence to innovations from Whitesides’ laboratory. Whitesides’ own collaboration with venture capitalists has led to the creation of many of them.

“The thing about George I really like is that he’s approachable and likable and always responds with discipline and energy. He’s open to ideas. He’s pretty unusual that way. Few others are as broadly based as he is,” says Benson, who recently received three potential inventions from the Whitesides Lab. One describes a way of injecting microfluidics for analytical study. Another involves the use of electrochemistry.

“[George] knows the whole process, but he’s not an expert on everything,” Benson adds. “He’s the first and most important channel, but you need people with patent skills and he’s surrounded himself with experts.”

However, Whitesides relishes his role as an educator and understands that no new technology will happen if nobody is there to discover the science.

“[Students] are, after all, the future,” says Whitesides. “A generation often believes the generations that follow aren’t quite as motivated, but in my experience, they are extremely competent and they are able to do anything you ask them to do. All you have to do is ask.”

—Paul Livingstone

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