f e a t u r e
Mathies moved on to Ithaca, NY, where he earned his Ph.D. at Cornell University in 1974. His mentor was Berkeley alumnus Andreas C. Albrecht (B.S. ’50, Chem), who is considered by many to be the father of the theory of resonance Raman spectroscopy. “Albrecht was a brilliant but understanding mentor who allowed me to take time off for some major outdoor expeditions,” says Mathies. On the wall behind his desk hangs a large photograph of Mathies climbing the Devils Thumb, a rock spire jutting out of the Stikine Ice Cap near Petersburg, AK. The 9,077-foot peak features a near-vertical, 6,000-foot face — twice as tall as Yosemite’s El Capitan with ice and snow and horrific weather — that has taken the lives of several climbers. Mathies and his partners scaled the peak from the east, as did the climbing author Jon Krakauer, who completed the first solo ascent of the mountain following a similar route. Back in civilization, Mathies won a Whitney fellowship to Yale University to work with Lubert Stryer, who three decades later would win the 2006 National Medal of Science for his work on fluorescence spectroscopy and the biochemical basis of signal amplification in vision. Mathies’s postdoc with Stryer was his first foray into the life sciences, a path he would explore more fully later in his career. Mathies came to the College of Chemistry in 1976 as an assistant professor and spent the first 10 years as a biophysical chemist focusing on Raman spectroscopy and understanding the molecular basis of the primary events in vision. Former Mathies student Christina Stuart (Ph.D. ’07, Chem), who is on her way to a postdoc at UC San Diego, explains the group’s work this way: “Raman spectroscopy is a vibrational technique that provides information on the structure of molecules. In Raman spectroscopy, a sample is irradiated with laser light. A small number of the laser photons imparts energy to the molecules, exciting them into a higher vibrational state. The resulting Raman-scattered light now has a frequency which is shifted from that of the incident light. The difference in these frequencies corresponds to a vibrational frequency of the molecule, which tells us about its structure.” In 1984 Mathies embarked on another adventurous path when he filed his first patent — an infant carrier that he designed with wife JoAnne. “It was a good design, but it was never commercialized,” he says. “I still have the prototype in my garage.” The next 34 patents would prove to be more successful. By the late 1980s, the revolution in genomics was in full swing. Biotech pioneers such as Genentech, Chiron and Amgen — all UC spin-offs — were growing, along with a host of smaller companies. With the beginning of the Human Genome Project slated for 1990, Mathies and his students began exploring the utility of laser spectroscopy techniques for biomolecular detection. Stephen Fodor was a postdoc in the Mathies group at that time who used Raman spectroscopy to elucidate the photoactivation of bacterial and plant photo receptors. Intrigued by the applications of
laser spectroscopy to genomics, Fodor in 1989 took a position at the Affymax Research Institute in Palo Alto, where he spearheaded the effort to develop high-density microarrays of biological compounds. Fodor also developed techniques to read these arrays, employing fluorescent labeling methods and confocal laser scanning. Four years later, Fodor co-founded Affymetrix, a company that has developed technology to synthesize many varieties of high-density arrays containing hundreds of thousands of DNA probes. These DNA chips have broad commercial applications and are now widely used in many areas of basic and clinical research. Says Mathies, who serves on the scientific advisory board of the company, “It was Affymetrix that got the whole gene chip technology going.” The company is just one of 10 start-ups in which Mathies has played a role. One company, ACLARA Biosciences, pioneered labon-a-chip microfluidic arrays for high-throughput pharmaceutical drug screening and gene expression analysis. Another start-up, Molecular Dynamics, developed integrated systems that combined laser-scanning, electro-optical and software technologies to produce bioanalytical instrumentation and DNA sequencing systems. In the 1990s, Mathies’s patents on fluorescent probes began to bear fruit for Berkeley, earning almost $1 million dollars annually in licensing fees by the end of the decade. It was also in the 1990s that Mathies began working on the microfabrication of lab-ona-chip devices. The Mathies group started this work in 1992, and it led to miniaturized devices that could perform DNA bioanalytical work. Says Mathies, “We put together a group A schematic of a microfluidic device. of smart, brave, hard-working people doing new things. I was so lucky to be part of that.” Adam Woolley, now an associate professor at Brigham Young University, earned his Ph.D. with Mathies in 1997. Says Woolley, “I had the great fortune to work with Rich at a very exciting time: the Human Genome Project was at an early stage as I was starting graduate school at Cal. Rich gave me broad latitude to work in his lab to develop a revolutionary DNA sequencing technology at the interface
Spring 2008 Catalyst