The whole package: A lifetime of science

As a junior chemistry major at Reed College, Christopher Mathews read Currents in Biochemical Research 1956, a compendium of 27 essays that charted the present course of biochemical research and considered the intimate relationship of biochemistry to medicine, physiology and biology. He was hooked.

The not-so-light reading compelled him on a journey of a lifetime, from researcher, teacher, mentor, department chair, distinguished emeritus professor and lifelong scientist. He has earned a reputation as an internationally recognized leader in biochemistry with an extensive record of research focused on enzymology, virology, and genetics. Mathews has received significant attention for his work with nucleotide and coenzyme metabolism, DNA synthesis and replication and nucleic acid enzymology.

In November, he will be recognized with the College of Science’s 2017 Lifetime Achievement Award in Science.

Chris Mathews, Distinguished Emeritus Professor of Biochemistry & Biophysics

Mathews exudes many of the characteristics often associated with Pacific Northwesterners—tenacious, conscientious, innovative, open-minded and deep thinking—despite the fact of being born in New York City. His family moved to Olympia, Washington in 1949.

In 1957, Mathews had just decided to pursue a career in biochemistry. As he weighed his options on which doctoral program to attend, he recalls a pivotal moment while visiting his grandparents back East after his junior year. He was touring top East Coast graduate departments and Brookhaven National Laboratory. His host, Dr. Robert Steele, asked, “Why are you considering universities in the East, when one of the best biochemistry departments in the country is right in your own backyard, in Seattle?”

So in 1958 after graduating from Reed, he began the doctoral program in biochemistry at the University of Washington, supported by a prestigious Woodrow Wilson Fellowship that identifies and develops leaders to meet the nation’s critical challenges.

Mathews delights in recalling his visit to UW where he met Ed Krebs, who gently reminded him that he was not Krebs of the Krebs Cycle that is part of cellular respiration. That would be Hans Krebs. But, adds Mathews, who would have predicted nearly 35 years later that Ed Krebs would become as famous as Hans, when he and Eddie Fischer would share the Nobel Prize for discovering protein phosphorylation, work that was underway in Seattle at that very moment of Mathews visit in 1957.

His life was filled with many such serendipitous meetings and moments.

He met and married fellow biochemistry student Catherine Zitcer, and the couple soon became parents to their first child, Lawrence. Mathews began publishing at UW, authoring a paper that was acclaimed as a success from the biochemistry community.

He found a place in the laboratory of Dr. Frank Huennekens, who studied folate coenzymes and one-carbon metabolism. Mathews found the idea of targeting drugs to treat disease exciting. He worked with Huennekens on an introductory project that resulted in his first publication in the Journal of Biological Chemistry in November 1960.

Mathews became interested in genetic biochemistry after attending a series of talks from visiting lecturer Erwin Chargaff —the Austro-Hungarian biochemist from Columbia University whose work led to the discovery of the double helix structure of DNA. A former of Chargaff’s, Seymour Cohen, was doing groundbreaking work on the induction of new enzymes in bacteria infected with T-even bacteriophage. His work would offer the first systematic exploration of the biochemistry of virus-infected cells and of how viruses multiply. Much of Cohen’s research has contributed to the chemical treatment of cancer and viral infections.

From reading Cohen’s papers, Mathews learned that the work provided an excellent link between Mathews’ own training with Huennekens and the more biological work he hoped to do.

In January 1962, the newly minted Ph.D., his wife Kate and their infant son, Lawrence, made the long, snowy drive from Seattle to Philadelphia, where he began work in Cohen’s lab at the University of Pennsylvania. Then in late 1963, Mathews accepted his first faculty position as Assistant Professor of Biology at Yale University in New Haven, Connecticut, soon after he and Kate welcomed their daughter Anne.

Four years later, he encountered a tuning fork in the road. Just as he was contemplating his future, his department chair enlightened him:  if he aspired to be a full professor at Yale, he would need to be recognized as one of the top 50 biologists in the country. He was carrying his colleague Wyatt’s teaching load while he was on sabbatical as well as his own course load and his premedical advising duties. He thought the plan his chair laid out seemed unrealistic.

Mathews jumped at the chance to become involved in a new academic enterprise and moved to the University of Arizona in Tucson in 1967, just in time to meet its first class of 32 medical students. He relished the opportunity to have a broad impact on the institution.

With data from Yale plus experiments in his new lab, Mathews published, the first research article from the University of Arizona College of Medicine in the spring of 1968.He and his colleagues significantly advanced the study of regulation of deoxyribonucleoside triphosphates (dNTPs), the building blocks for DNA replication.

“That is when I learned that I was in love with the whole package,” said Mathews. “Where most professors can prosper by full engagement with research or teaching or leadership, I found a need to be involved with all threefull engagement with all three.”

In 1977, Mathews was recruited for chair of the Department of Biochemistry and Biophysics at Oregon State University. He was attracted by the prospect of a 14-person faculty of active researchers and valued an atmosphere of collegiality and mutual respect. In January 1978, the Mathews family moved to Corvallis, their home for 40 years and counting.

He learned the importance of securing external funding to support the whole enterprise, not just his own research. He recalls when he submitted a proposal for an NIH training grant and received a mediocre score. But, he notes with his trademark good humor, on the pink sheet was written, “The training record of the faculty is not impressive; most of the graduates have taken positions in industry.”

Mathews appealed to NIH, pointing out that Congress, as the funder of NIH, might not like to hear that NIH reviewers considered careers in industry second-rate. His next several training grant proposals were funded.

In 1981, he submitted a large proposal to a regional foundation to upgrade molecular genetics on campus that was successful. OSU was a pioneer in creating an interdisciplinary center that supported molecular genetics through a service laboratory, recruited faculty with joint appointments and offered them a second intellectual home. The center eventually became the Center for Genomic Research and Biocomputing (CGRB), which today facilitates genome-enabled and data-driven research in the life and environmental sciences at OSU and across the state. Today, more than 120 OSU faculty are affiliated with Center.

Over nearly five decades, Mathews and his 35 Ph.D. students, postdocs, research assistants and 150 undergraduate students explored looming questions in the field of regulation of DNA precursors.

This fall, one of Mathews’ former undergraduate students, Marian Waterman spoke at CGRB’s annual conference. Waterman is the Director of the Center for Cancer Research at the University of California-Irvine where she conducts research on cell signaling.

In the mid-1980s, Mathews and colleague Ken van Holde collaborated to write their first biochemistry textbook. It was tailored to their one-year majors’ course, and also accomplished an even loftier task:  to define biochemistry as a discipline.

“In an era when biochemistry seemed to be losing its identity vis-à-vis other molecular life sciences……I believed that biochemistry was and is a distinct discipline, although it intersects with all of the life sciences. I wanted to attempt to define that discipline,” explained Mathews.

Approaching the “traditional retirement age” of 65, Mathews remained zealous about teaching and research. But after serving as department chair for more than eight three-year terms, he turned over the reins of leadership to a colleague, enabling the department to hire a new faculty while he continued to contribute as an emeritus professor.

Although Mathews “retired” in 2002, he did not close his lab. He reset, reenergized and renewed his involvement in his lab, conducting his own experiments again. The work led him to a growing realization that dNTP metabolism is linked with processes as distinct as mutagenesis, cell cycle progression, DNA damage, and oncogene and tumor suppressor action. His latest work has led to collaborations with more than 10 laboratories and resulted in a dozen joint publications since his “retirement.”

In 2012, Mathews closed his lab, which had enjoyed external research funding for more than 48 years at three different universities. No small feat by any measure even in the best of times. Since then, he has served as lead author of the textbook Biochemistry, published in 2012 in its fourth edition with a new co-author.

“It is the stimulation of ideas and the contact with students that are satisfying as an emeritus professor,” said Mathews when asked how he remains intellectually stimulated.

In 2014, Mathews published Biochemistry: Concepts and Connections with two coauthors. The book has been praised as a highly visual, fresh approach to guide science majors toward a deeper understanding of biochemistry that will better prepare them for the challenges of 21st century science through quantitative reasoning skills and a rich, chemical perspective on biological processes.

Today, Mathews teaches one or two courses each year, reviews journal articles and is working on a new textbook. He continues to be widely cited in the current scientific body of literature.

Upon reflection over the course of his career, Mathews believes he has been fortunate to have had “the whole package.”

Reflecting back on his successes, he and Kate decided to make a legacy gift, thanks to a wise real estate investment, that would support and inspire future generations of biochemists at Oregon State. In 2015, they established the Christopher and Catherine Mathews Graduate Fellowship, which is based on academic merit, teaching acumen and research potential.

The gift has been leveraged through the Provost Graduate Fellowship Match Program, a partnership between the OSU Foundation, the Biochemistry and Biophysics Department and the Graduate School. The endowed fellowship enables the department to recruit and retain extraordinary doctoral students by supporting a student in their second year.

“Looking back, I think that I have embraced the whole package, as I originally wished to do,” said Mathews. “For me, all of the stars were aligned.”

Note:  Based on an interview with Christopher Mathews and his autobiographical reflection that appeared in the Journal of Biological Chemistry in May 2008.

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