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The History of Biochemistry ISSN 2409-4943. Ukr. Biochem. J., 2021, Vol. 93, N 2 THES HHISI TORY OF BBIOCHEMISIOCHEMISTRY UDC 577.213.3 doi: https://doi.org/10.15407/ubj93.02.116 DOUBLE NOBEL PRIZE WINNER: FREDERICK SANGER – THE FATHER OF GENOMICS T. V. DANYLOVA1, S. V. KOMISARENKO2 1National University of Life and Environmental Sciences of Ukraine, Kyiv; e-mail: [email protected], 2Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv; e-mail:[email protected] Received: 02 February 2021; Accepted: 23 April 2021 This paper aims to outline briefly the main stages of Frederick Sanger’s scientific activity – the only person to have won two Nobel Prizes in Chemistry (1958, 1980). His work on the structure of proteins, es- pecially that of insulin, and the determination of base sequences in nucleic acids made an immense impact on the development of biochemistry and especially on the development of a new scientific field – molecular biology. His methods for determining the primary structure of proteins and nucleic acids helped biochemists and molecular biologists to determine the structure of many proteins and nucleic acids and laid the basis for genetic engineering. K e y w o r d s: Frederick Sanger, Nobel Prize, insulin, proteins, nucleic acids, Sanger’s method of DNA se- quencing. he Nobel Prize is considered the highest England).­He­was­the­middle­child­in­the­family­of­ honor­­in­the­scientific­community.­Reflecting­­ Frederick Sanger, a country medical doctor, and his T the highest achievements one can attain in wife­Cicely­Sanger­(née­Crewdson),­the­daughter­of­ socie ty, it has become more than just a prize – it a wealthy cotton manufacturer. Cicely and Frederick provides worldwide recognition, respect, and pres- Sanger had three children: Theodore was born in tige. It is a great honor to deliver a Nobel lecture, 1917, Frederick – in 1918, and Mary – in 1923. and even a greater honor to deliver it twice. Be- All children were brought up as Quakers as tween 1901 and 2020, 934 Laureates and 28 organi- their father was a devoted religious man active in zations have been awarded the Nobel Prize. Four the­Society­of­Friends­[5].­The­children­were­taught­ scientists obtained a Nobel Prize twice – Marie such­ values­ as­ truth­ and­ hard­ work­ that­ defined­ Skłodowska­Curie­(Physics­­1903,­Chemistry­1911),­ Frederick’s personality. Even when he no longer fol- Linus­Pauling­­(Chemistry­1954,­Peace­1962),­John­ lowed Quaker belief, these personal traits remained. Bardeen­(Physics­­1956,­Physics­1972),­and­Frederick­ When Frederick was 5 years old, his family moved Sanger­(Chemistry­1958,­Chemistry­1980)­[1].­Frede­ in Tanworth-in-Arden, which was closer to Bir- rick­Sanger­and­Linus­Pauling’s­scientific­creativity­ mingham.­His­early­schooling­was­taken­care­by­a­ was directly related to the central focus of generating Quaker governess. At the age of nine, he went to the new­Life­Science­knowledge­[2].­This­paper­we­de- Downs School – a Quaker boarding school. In 1932, vote­to­Frederick­Sanger­and­his­scientific­legacy. Frederick moved as a boarder to Bryanston, Dorset. Frederick Sanger was born on August 13, The liberal education there had a huge im- 1918,­in­the­village­of­Rendcomb­(Gloucestershire,­ pact on Frederick. Being introduced to the joy of © 2021 Danylova T. V., Komisarenko S. V. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 116 T. V. Danylova, S. V. Komisarenko the University of Cambridge as an undergraduate , I had to decide which three scientific subjects I should take. I had chosen two-and-a-half subjects and was looking through the list of “half” subjects when I noticed one I had not heard of before: “Biochemis- try, supervisor Ernest Baldwin”. The idea that biolo- gy could be explained in terms of chemistry seemed an exciting one, and this was amply confirmed when I met the enthusiastic Dr. Baldwin”­[7].­ Ernest Baldwin was a member of the Biochemistry Department of the University of Cam- bridge established by an English biochemist Frede- rick Gowland Hopkins – the Nobel Prize winner in Physiology or Medicine 1929 for the discovery of­vitamins­[8].­Hopkins­had­the­enthusiastic­sup- port of his younger colleagues. Joseph and Dorothy Frederick Sanger [3] Needhams dubbed him the Fundator et Primus Ab- bas­of­biochemistry­in­England­[9].­In­1961­during­a­ Symposium on Biochemistry and Nutrition to celeb- science and having a good rapport with his biol- rate­the­centenary­of­the­birth­of­Frederick­Gowland­ ogy master Frazer Hoyland and chemistry master Hopkins,­Joseph­Needham­stated:­“our meeting to- Henry Geoffrey Ordish, he was involved in biol- day symbolizes the feeling of discipleship which we ogy­and­chemistry­­clubs­[6].­Doing­well­at­school,­ all have for Frederick Gowland Hopkins, essentially he­passed­the­School­Certificate­exams­on­seven­ the founder of modern biochemistry in our country” subjects­that­quali­fied­him­for­entry­to­Cambridge­ [10].­When­Frederick­Gowland­Hopkins­retired,­Jo- University.­In­1936,­he­was­accepted­by­St.­John’s­ seph Needham moved out of biochemistry to focus College. Frede rick’s parents had been hoping their on his other scope of interest – Chinese civiliza- son would follow his father’s footsteps by studying tion and science. The Department of Biochemistry medicine.­However,­a­young­student­abandoned­the­ headed­­by­Hopkins­became­an­interesting­­and­ex- idea as he believed that science would provide him citing­place­for­Frederick­Sanger.­As­he­expected,­ a more suitable lifestyle and would not be so time- it was here where he had a chance to acquire the consuming. necessary fundamental knowledge on living matter In Cambridge for Part I of the Natural Scien ces for­solving­problems­in­the­field­of­medicine.­ Tripos, Frederick Sanger took chemistry, physics , During his second year at the University, and­math­and­biochemistry­as­half­subjects­[6].­Ex- Frede rick dropped physics and chose to study plaining his choice of biochemistry, terra incognita physio logy instead, keeping his studies in chemis- for­him­at­that­time,­Sanger­wrote:­“When I arrived at try, biochemistry , and math, which he was not happy with.­He­liked­biochemistry­most­and­it­became­the­ subject­for­Part­II­of­the­Tripos­[5,­6].­ In 1936, Frederick Sanger joined the Cam- bridge­ Scientists’­ Anti­War­ Group­ –­ a­ left­wing­ pacifist­group­founded­in­1932­to­campaign­against­ militarism.­Joseph­Needham­–­one­of­his­lecturers­ in­biochemistry­–­was­also­a­member­of­the­Group.­ Sanger’s­ religious­ background­ to­ a­ large­ extent­ shaped­his­pacifist­views.­Here­he­met­his­future­ wife Joan Margaret Howe. She was an economics student at Newnham College. They married in 1940 and remained married until her death in 2012. They had­three­children­–­Robin­(1943),­Peter­(1946),­and­ Mary, Frederick and Theodor Sanger [4] Sally­Joan­(1960).­Frederick­Sanger­ascribed­his­wife­ 117 ISSN 2409-4943. Ukr. Biochem. J., 2021, Vol. 93, N 2 a n­key­role­i ­his­successful­career,­saying:­“Although laureates­in­chemistry­[13],­prompted­him­to­begin­ not a scientist herself she has contributed more to work on determining protein structure. my work than anyone else by providing a peaceful Using insulin as a model for study, Sanger de- and happy home”­[11]. veloped a new method for analyzing the structure In 1939, he graduated in biochemistry from of proteins and showed that the insulin molecule St.­John’s­College,­Cambridge.­Earning­a­First­on­ is composed of two peptide chains referred to as his­biochemistry­exam,­he­was­surprised.­Being­a­ the A chain and B chain. They are linked together modest­person,­Sanger­wrote:­“I was not academi- by­two­disulfide­bonds,­and­in­most­species,­the­A­ cally brilliant. I never won scholarships and would chain consists of 21 amino acids and the B chain of probably not have been able to attend Cambridge 30­amino­acids.­Benefiting­from­the­method­of­pa- University if my parents had not been fairly rich…” per­chromatography,­Sanger­identified­unmodified­ [7].­During­World­War­II,­a­tribunal­granted­Sanger­ amino­acids­[14,­15].­It­took­him­years­to­definitively­ conscientious objector status and he became an or- identify 51 amino acids in the molecule of this pro- derly at a military hospital near Bristol. Frederick tein­hormone­[16].­ went to Cambridge to become a research student. As F. Sanger worked out the sequence of 30-resi- far­as­he­did­not­need­university­financial­support,­he­ due-long B chain together with the Austrian scientist gained­admission­[5].­He­started­his­PhD­in­October­ Hans Tuppy and 21-residue-long A chain with Ted 1940 under the supervision of Norman Wingate (Bill)­ Thompson,­a­PhD­student­from­Australia­[17­21].­ Pirie.­He­aimed­to­investigate­whether­edible­protein­ In 1955, Sanger completed his investigation on could­be­obtained­from­grass.­However,­Pirie­left­the­ the insulin sequence, and his work later became the department, and Albert Neuberger was assigned as basis for the production of synthetic insulin and oth- Frederick’s new mentor. Sanger changed his the- er hormones. From 1944 to 1951, Frederick Sanger sis­title­and­worked­on­the­topic­“The metabolism held­a­Beit­Memorial­Fellowship­for­Medical­Re- of the amino acid lysine in the animal body”­[12].­ search and since 1951 he has been a member of the Describing­­the­beginning­of­his­scientific­journey,­ External­Staff­of­the­Medical­Research­Council. Sanger­stated:­“I regard Albert as my main teacher. In 1958, Frederick Sanger received the Nobel The most important thing he taught me, both by in- Prize­in­Chemistry­“for his work on the structure struction and by example, was how to do research.
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