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Herbert ‘Freddie’ Gutfreund obituaryWorld-leading expert on enzymes whose colleagues at Cambridge’s

colleagues at Cambridge’s fêted Laboratory of Molecular Biology included Crick and Watson

Gutfreund experimenting with nitrogen at Imperial College London in 1943

UNIVERSITY OF BRISTOL


Freddie Gutfreund was supping a lunchtime pint at the Eagle pub in Cambridge in February 1953 when Francis Crick burst in to announce that he had solved the secret of life. Having witnessed the febrile excitement of his friend, who with James Watson discovered the structure of DNA, Gutfreund would go on to make not insignificant scientific discoveries himself on the structure and function of proteins.

Gutfreund’s principal achievement was to develop techniques to identify and characterize the catalyzed reactions of enzymes. In order to observe constantly moving and shape-shifting protein molecules by the millisecond, Gutfreund developed his own rapid reaction equipment. “If you build your own machine, you can do an experiment that no one else can,” he said.

Key advances in the understanding of glycolysis (the breakdown of glucose) and muscular contraction have emerged from these studies. Among the reagents he discovered are many that provide the basis for drugs to treat diseases such as muscular dystrophy and cystic fibrosis, caused by proteins that are inactive or overactive. The reagents Gutfreund developed would enable the proteins to do their job. He also devised methods for looking at enzymes involved in breaking down blood sugar, leading to the development of drugs to treat diabetes.


Many of his discoveries were inspired by his close proximity to the scientists who formed the star-studded Laboratory of Molecular Biology at Cambridge, comprising eight future Nobel laureates, including Crick, Watson, Fred Sanger, and Peter Mitchell.


Scurrying between these brilliant older scientists like an excited puppy, Gutfreund would pass the information on what the others were doing and receive valuable insights in return. “Freddie always showed us that science was a social as well as an academic activity,” said Mike Geeves, professor of biochemistry at the University of Kent, who worked under Gutfreund as a Ph.D. student at Bristol University. “These days we would call him an influencer, a human catalyst or perhaps more appropriately an enzyme, stimulating ideas, cross-fertilizing lots of activity.”


He acquired the nickname Freddie at Cambridge and was born Herbert Gutfreund into a middle-class family in Vienna in 1921 to Clara (née Pisko) and Paul Gutfreund, a civil engineer. An early love of physics was encouraged by his mother’s cousin, Karl Weissenberg, a theoretical physicist who made notable contributions to crystallography and rheology. In sessions with “Uncle Carli”, he learned about the electron structure of atoms. Aged 12, he set up experiments to make synthetic rubber and plastic glass. “I heated a lot of things in a crucible. I also had plans to build a television set. I knew even less about the latter than the former, but got no further than making a box,” he recalled.


He hated school, recalling that botany classes were “less interesting than my stamp collection”. After passing his high school diploma in Vienna (equivalent to the 11-plus) he would not gain another qualification until being awarded a doctorate at the University of Cambridge 15 years later. “I succeeded because my mind was not prejudiced by irrelevant facts,” he later wrote. “It helped me to do original work.”


With his father unemployed during the Depression, Gutfreund mixed school with part-time work in the Colloid research laboratory of the Semperit Rubber Company, analyzing the components of rubber latex.


His ambitions in Austria were quickly thwarted after the Anschluss in 1938. Freddie’s paternal uncle would be murdered at Auschwitz and several other Jewish relations died in the Holocaust. As the streets of Vienna echoed to the sound of Nazi jackboots, Gutfreund noted that a scheme being run by the YMCA, “British Boys for British Farms”, was accepting candidates from Europe because of the lack of British applicants for farm work.

At Cambridge flanked by Francis Crick, left, and James Watson


At Cambridge flanked by Francis Crick, left, and James Watson


While he was working as a dairyman on a farm in Westmorland, now in Cumbria, the public library in Kendal became his best friend. He mastered English fast. He found seasonal work doing pH measurements in a Milk Marketing Board cheese factory in Aspatria (then in Cumberland) and was subsequently accepted as a “lab boy” in the department of pathology at Liverpool University. Gutfreund impressed HJ Channon, the university’s professor of biochemistry. “He had serious quarrels with people, but he looked upon me as somebody who deserved support,” Gutfreund recalled. With Channon’s patronage, he developed electrodecantation, a process to separate proteins of different charges. This work, while still a lab technician, led to Gutfreund’s first publication in the Biomedical Journal. He was then packed off to Oxford by Channon with samples of treated plasma to work at the only ultracentrifuge (a rotor that spins a substance at high speed to separate different components) in operation in England, under Dr AG “Sandy” Ogston, a fellow of Balliol College.

Channon later recommended Gutfreund to AC Chibnall, professor of biochemistry at Imperial College London. Here, the 21-year-old joined the protein chemistry group as a research assistant in January 1943. Chibnall was trying to determine the molecular weight of insulin. Gutfreund’s solution to that problem proved to be his passport to Cambridge. One year later Chibnall took up the chair of biochemistry at the university, stipulating that Gutfreund, as his assistant, be allowed to register for a research degree in Cambridge.


Gutfreund’s Ph.D. at Fitzwilliam College was on the reversible dissociation of proteins (separating them into atoms, ions, or radicals). Here, he came to know Sanger, who had developed the method to visualize one-dimensional structures of proteins, giving Gutfreund the basis of protein chemistry that would be essential for his work. Other influences were Alan Hodgkin and Andrew Huxley, who established a model for nerve conduction (the speed of electrical impulses moving through the nerve); Hugh Huxley and Jean Hanson, who established the sliding filament model (the process used by muscles to contract); and John Kendrew and Max Perutz, who solved the first three-dimensional structures of proteins. Along with Crick and Watson, the group formed the Laboratory of Molecular Biology.


Gutfreund was awarded his doctorate in 1947 without having taken a BSc or MSc and would continue his research at Cambridge. By then he had acquired the name Freddie when a visitor to his lab asked a question and was told “ask Freddie over there”. The name stuck.

Crick remained one of his closest compadres and benefited from the intelligence Gutfreund gleaned from his correspondence with the eminent American scientist Linus Pauling, who was competing with Crick and Watson to make the breakthrough on the structure of DNA.

Gutfreund would lunch with Crick and Watson and continued discussions on their post-prandial walks. He took the famous photograph of the pair by King’s College Chapel.


A keen cook, he hankered to prepare exotic dishes but could not do so in his tiny digs. Crick allowed Gutfreund to use the kitchen at his home, “the Golden Helix” at 19/20 Portugal Place. It became a laboratory of culinary exploration for a young man reveling in the availability of more exotic ingredients after years of wartime austerity. Crick, his wife, Odile, and their friends shared the results. George Kistiakowsky, the visiting physical chemistry professor from Harvard who had been involved in developing the atomic bomb, noted after a dish of Oiseaux sans tête washed down with more than passable claret: “Freddie, you are wasting your time in science.”


Gutfreund had started what he called his “first proper job” in 1956 at the National Institute for Research in Dairying at Shinfield, then part of the University of Reading. At Shinfield, he met Mary Davies, a zoologist. They were married in 1958. She survives him along with their children: Philippa, a chartered accountant, Nick, a furniture designer, and Peter, a marketing consultant.


He set up the Molecular Enzymology Laboratory at Bristol University in 1965, where he became recognized as a world leader in the study of enzymology and protein chemistry. In 1981 he was elected a fellow of the Royal Society and officially retired in 1986. During 20 years at Bristol, he launched many scientific careers. It was payback for all the opportunities he was given despite his lack of qualifications. He liked to say: “I would not have succeeded under the educational system of the 21st century.”


Throughout those formative years of scientific discovery at Cambridge, his relationship with Crick was mainly that of mentor and protégé. However, Gutfreund did once contradict the accepted theory that biological structures, especially proteins, were static entities, shouting, “But they move”. Crick was initially doubtful and for a time referred to the concept as “Freddie’s little red herring”, but later graciously acknowledged that his friend was right.


Herbert “Freddie” Gutfreund, the scientist, was born on October 21, 1921. He died on March 21, 2021, aged 99

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