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John Clark Sutherland and Betsy Blake Middleton met on a blind date in the fall semester of 1961. John was a senior at Georgia Tech while Betsy was a freshman at Emory University. They were inseparable after meeting. While their majors were different, they would study together all the time.

In spring 1962, John graduated with a bachelor’s degree in physics.

In spring 1964, Betsy graduated with a bachelor’s degree in biology and enrolled for a master’s degree at Emory. John completed a master’s degree in physics and began studying for the Ph.D. comprehensive exams in physics at Georgia Tech. He studied in the biology department at Emory because Betsy was going to class there and also teaching.

John passed the Ph.D. comprehensive exams at Georgia Tech in June 1965 and started working with James R. Stevenson, on the optical properties of alkali metal at short wavelengths. He applied and received a predoctoral fellowship from the Oak Ridge Associated Universities and moved to Oak Ridge National Laboratory to do his research in the Health Physics Division under the supervision of E. T. Arakawa.

John and Betsy got married in August 1965, shortly after Betsy completed her master’s degree, under the supervision of Charles Ray, a protozoologist. She was writing her master’s thesis while planning their wedding. Betsy started Ph.D. work with Richard F. Kimball, a protozoologist at Oak Ridge National Laboratory who also had a faculty appointment at the University of Tennessee, Knoxville.

Betsy and John focused on their own sciences while doing their Ph.D. research at Oak Ridge National Laboratory. They lived in Oak Ridge, in the third floor of an apartment block affectionately known as “The Bricks.” Rent was $62.50 a month. 

Betsy collaborated with Richard B. Setlow, a physicist who was one of the pioneers in the study of DNA damage by UV radiation and repair. Setlow and others had shown that bacteria can naturally repair the DNA damage caused by UV light. For her dissertation, Betsy showed that protozoa can do the same. Her 1968 Science paper was the first demonstration of photoreactivation in a eukaryote.

While Betsy was coaxing organisms called paramecia to demonstrate photoreactivation in eukaryotes, John was immersed in vacuum ultraviolet spectroscopy and radiation physics, understanding how radiation interacts with matter. One of his research achievements was showing that sodium is very close to being a free-electron metal. This finding contradicted earlier results, which were later shown to be artifacts.

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At Walter Reed Army Institute of Research, in Washington, D.C., Betsy and John Sutherland joined the laboratory of Friedrich Ernst Hahn in the Department of Molecular Biology as postdoctoral fellows. It was the only time in their careers that they worked together in the same lab full time.

Among the questions the couple examined is why certain molecules that insert between DNA bases in the helix prevent formation of pyrimidine dimers, which is the characteristic damage to DNA that UV radiation produces.

Others thought the inserting molecules prevent dimer formation by physically keeping the DNA bases apart. Betsy and John discovered that the effect is also due to excited-state energy transfer.

The work produced five papers with only Betsy and John as coauthors. It was made possible by John’s expertise in spectroscopy and Betsy’s ability to quantify pyrimidine dimers.

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From Washington, D.C., the Sutherlands headed West, for what John calls “real postdocs.” In hunting for jobs, they planned to be at least in the same city. Both got positions at the University of California, Berkeley, in labs associated with Nobel laureates.

At the University of California, Berkeley, John joined the lab of Melvin Calvin, the 1961 Chemistry Nobel Laureate. Because of Calvin’s interest in photosynthesis, the lab was focused on porphyrins. Thus did John – likely the only physicist in a building full of chemists – dive into porphyrin research, through circular dichroism (CD).

John inherited the magnetic CD instrument of Calvin’s former Ph.D. student Edward A. Dratz. He rebuilt the machine a few times and eventually hooked it to a computer.

Among John’s achievements during this period was a theoretical paper that resolved discrepancies in magnetic CD measurements of porphyrins reported in the Ph.D. dissertations of Dratz and Michael M. Malley, a Ph.D. student at the University of California, San Diego.

“Malley and Dratz knew each other,” John recalls. “They exchanged compounds to make sure they were working on identical material. They ensured that their magnets were properly calibrated. And they got hugely different answers.” By postulating a certain condition, John could explain everything that the graduate students found.

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Betsy joined the lab of Michael J. Chamberlin, a biochemist and molecular biologist at the University of California, Berkeley. With an NIH training grant, Betsy worked in the virology lab named after 1946 Chemistry Nobel Laureate Wendell M. Stanley, where she learned how to isolate and purify enzymes.

The skill positioned her to investigate closely the photoreactivating enzyme involved in DNA repair in eukaryotes, which are more complex than bacteria.

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After completing postdoctoral stints in the San Francisco area, the Sutherlands were poised to take on academic appointments, “real jobs,” as John puts it. As before, they looked for positions that allowed them to be at least in the same city. Their search brought them to southern California.

John joined the lab of Philip J. Stephens in the University of Southern California, Department of Chemistry as a research associate.

Betsy landed an academic appointment at the University of California, Irvine, Department of Molecular Biology and Biochemistry in 1972.

John’s academic appointment soon followed. In 1973, John joined the Department of Physiology and Biophysics in the College of Medicine of the University of California, Irvine. 

Betsy and John rose through the professorial ranks until they decided to move back East.

In 1972, Betsy landed an assistant professor appointment in the University of California, Irvine, Department of Molecular Biology and Biochemistry. Here Betsy began to examine repair of UV-induced DNA damage in human cells, with John as one of her collaborators.

Betsy’s solo 1974 Nature paper unequivocally established the existence of a photoreactivating enzyme in human leukocytes, which are a type of white blood cells. Prior to this paper, the data were contradictory.

Because photoreactivation mediates specifically the repair of UV-induced pyrimidine dimers, the enzyme can be used as a diagnostic tool: Any damage that the enzyme can repair must have been caused by UV-induced pyrimidine dimers. These dimers have been shown to cause death and mutation in simple unicellular organisms.

Given that UV light is known to produce skin cancer in humans, Betsy clearly thought that the dimers’ role in inducing cancers in humans had to be evaluated directly. But if humans lacked a photoreactivating enzyme, direct examination would require other means.

Betsy received tenure and was promoted to associate professor in 1975.

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John joined the Department of Physiology and Biophysics in the College of Medicine of the University of California, Irvine in 1973. “My initial start-up package was $23,000, an unheard-of high for the medical school,” John recalls.

At that time, the medical school was separated from the main campus, where Betsy was, by a parking lot and a cow pasture. John would have to cross the pasture to join Betsy for lunch, as he often did. They continued to collaborate in unraveling the workings of the photoreactivating enzyme.

John’s postdoctoral work in Berkeley on the magnetic CD of porphyrins got him started on the idea of a multifunctional spectrometer.

“I realized that one instrument can do both CD and magnetic CD, which tell you different things,” John recalls. “For a little incremental cost, you can greatly expand what an instrument can do.”

In Irvine, John began developing this idea. He came up with an emission and polarization spectrometer, which combined the ability to measure CD, magnetic CD, and fluorescence. Later, he would add more capabilities, culminating in the “FluoroDichroSpectroPhotometer.”

It’s the first of John’s instruments that can measure multiple properties in one spectral scan. 

Also at Irvine, John began designing computer interfaces for instruments. “In those days, you got signals from optical instruments on a chart paper,” John says. “Now all instruments are computerized, but when I set up my lab, you had to computerize them yourself.” One such computerized spectrophotometer John designed and built later enabled the measurement of the absorption spectrum of DNA at wavelengths greater than 300 nm.

John received tenure and was promoted to associate professor in 1976.

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In 1977, Betsy and John moved their labs to Brookhaven National Laboratory, in Long Island, New York. “Richard Setlow had moved to Brookhaven, and he recruited us,” John says. Yet the Sutherlands had just gotten tenured, and as John recalls, “We had a nice house in Laguna Beach with a view of Santa Catalina Island, a pleasant place to be.”
 

Going east was not an easy decision. What clinched the move, John recalls, was Betsy’s question: “Where can we get more done?” And John said, “At Brookhaven. Because Brookhaven is a research institution. You exist to do only research.”

Someone who remembers the “great migration” vividly is William H. Farland, then a postdoctoral fellow working with Betsy and John on photoreactivating enzymes in human cells. “I joined Betsy’s lab in 1976, and not much later I was told that the two labs were going to Brookhaven,” Farland recalls. “I could either join the move or find another place for a postdoc.” 
 

Except for one graduate student, everyone working with Betsy and John moved across the country, Farland says. “The opportunities on Long Island looked good.”

Packing, moving, and then restarting the labs in Brookhaven took about three months, Farland estimates. But he and his wife, Phyllis, had more to do than anyone else: They had to move a horse, belonging to Phyllis, who was a professional rider and trainer. The move was disruptive, Farland says, “but it was also a bonding experience. It brought the group closer.”