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Sir Edwin Mellor Southern FRS FRSE (born 7 June 1938)[4] is an English Lasker Award-winning molecular biologist, Emeritus Professor of Biochemistry at the University of Oxford and a fellow of Trinity College, Oxford. He is most widely known for the invention of the Southern blot, published in 1975[5] and now a common laboratory procedure.[6][7][8][9]

Key Information

Early life and education

[edit]

Southern was born in Burnley, Lancashire and educated at Burnley Grammar School.[3] He has a brother named John Southern and a sister Kay Monie. He went on to read Chemistry at the University of Manchester (BSc Hons., 1958). He continued as a graduate student (then Demonstrator, 1963) in the Department of Chemistry, University of Glasgow, where he was awarded his PhD in 1962.[10]

Career and research

[edit]

Southern is also the founder and chairman of Oxford Gene Technology. He is also the founder (in 2000) and chairman of a Scottish charity, The Kirkhouse Trust, which aims to promote education and research in the Natural Sciences, particularly the biological and medical sciences, and the Edina Trust, which was founded to promote science in schools.[11][12] These charities are financed using royalty income from licensing microarray technology.

Southern blot

[edit]

The Southern blot is used for DNA analysis and was routinely used for genetic fingerprinting and paternity testing prior to the development of microsatellite markers for this purpose. The procedure is also frequently used to determine the number of copies of a gene in the genome.[13] The concepts of the Southern blot were used in the development and creation of the modern microarray slide, which is an extensively used experimental tool. The northern blot, western blot and eastern blot, related procedures for the analysis of RNA, protein and post-translational modification of proteins, respectively, are all puns on Southern's name.

DNA microarray

[edit]

Southern founded Oxford Gene Technology (OGT) in 1995,[1] a company that developed DNA microarray technology. OGT won a 1999 patent infringement lawsuit against Affymetrix based on his patent holdings in microarray technology.[14]

Awards and honours

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In 1990, Southern was one of the winners of the Gairdner Foundation International Award.[15] In 1998 he was awarded the Royal Medal of the Royal Society of London.[16] He received the Association for Molecular Pathology Award for Excellence in Molecular Diagnostics in 1999.[17] He was made a Knight Bachelor in the June 2003 Birthday Honours for services to the development of DNA microarray technologies. In 2005 he was awarded the prestigious Albert Lasker Award for Clinical Medical Research,[4][18] jointly with Alec Jeffreys of the University of Leicester for his invention of the Southern blot.[19] In 2005 he was also awarded the Association of Biomolecular Resource Facilities Award for outstanding contributions to Biomolecular Technologies.[20] In 2012, he was elected an Honorary Fellow of the Royal Society of Edinburgh.[21] His nomination for the Royal Society reads:

Dr. Southern has done pioneering work on the organization of DNA sequences in chromosomes. Apart from studies on crab poly-AT carried out in the early 1960s, Southern was the first to determine the nucleotide sequence of a eukaryotic chromosomal DNA fraction, demonstrating that a guinea pig 'satellite' had an unexpectedly simple repetitive structure based on a sequence of six nucleotides. In mouse satellite DNA he showed both short and long range periodicities. These and other studies on repetitive DNA he showed both short and long range periodicities. These and other studies on repetitive DNA sequences enabled him to suggest how non-coding chromosomal DNA may have evolved. Southern has devised valuable methods for DNA analysis. His 'blot' technique, for the identification of specific sequences among large populations of fragments generated by endonucleases, has found extremely widespread and important applications. He has also made important observations on the differential transcription of DNA sequences into RNA, and on patterns of DNA methylation.[22]

References

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Edwin Southern

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Sir Edwin Mellor Southern FRS (born 7 June 1938) is an English molecular biologist best known for inventing the Southern blot, a seminal technique in molecular biology that enables the detection and analysis of specific DNA sequences.[1][2] Born in Burnley, Lancashire, Southern attended Burnley Grammar School before pursuing higher education in chemistry at the University of Manchester, where he earned a BSc with honours in 1958.[3][2] He continued his studies as a graduate student in the Department of Chemistry at the University of Glasgow, obtaining a PhD in 1962.[4][2][5] Early in his career, Southern shifted from radiation chemistry to molecular biology, joining the Medical Research Council (MRC) Mammalian Genome Unit in Edinburgh in 1967 under Peter Walker.[6] There, he contributed to early efforts in sequencing eukaryotic DNA and studying satellite DNAs, leading to the development of the Southern blot technique in 1973, which he published in 1975.[6][7] This method, involving the transfer of DNA fragments from agarose gels to nitrocellulose membranes for hybridization with probes, became a cornerstone for gene mapping, diagnostics, and forensic science, including DNA fingerprinting.[1][8] In 1985, Southern was appointed to the Whitley Chair of Biochemistry at the University of Oxford, a position he held until his retirement in 2005, while also serving as an Honorary Fellow of Trinity College.[7][9] At Oxford, he pioneered oligonucleotide microarray technology in the early 1990s, advancing high-throughput DNA analysis and contributing to the Human Genome Project's physical mapping efforts.[6][1] In 1995, he founded Oxford Gene Technology (OGT), a company focused on genomic applications, where he later served as Chief Scientific Officer.[9][7] Southern's innovations have had profound impacts on genomics, enabling widespread applications in research, medicine, and agriculture.[8] He has also applied his expertise philanthropically, establishing the Edina Trust in 2002 to promote science education in UK schools and the Kirkhouse Trust in 2000 to support research on disease-resistant crops for subsistence farmers in Africa and India, funded by royalties from his microarray patents.[6][4][10] His contributions have been recognized with numerous honors, including election as a Fellow of the Royal Society in 1983, the Gairdner Foundation International Award in 1990, the Royal Medal of the Royal Society in 1998, and the Albert Lasker Award for Clinical Medical Research in 2005 (shared with Sir Alec Jeffreys for advancements in DNA analysis).[1][11][8] He was knighted in the 2003 Birthday Honours for services to the development of DNA technology.[12]

Early life and education

Early life

Edwin Southern was born on 7 June 1938 in Burnley, Lancashire, England, to working-class parents in a council house typical of the region's modest post-war housing. Burnley, a cotton town in the industrial heart of northern England, was marked by economic hardship in the 1940s, with textile mills dominating the landscape and providing limited opportunities amid rationing and reconstruction efforts following World War II. This socioeconomic context, characterized by a blend of factory work and small-scale entrepreneurship, shaped Southern's formative years, fostering resilience and a practical approach to problem-solving in a community where access to higher education was rare for those from similar backgrounds.[13] Southern's family exemplified the working-class dynamics of the area, with limited details available on his parents' occupations beyond his father's role as a typewriter repairer who enjoyed inventing tools and gadgets. This paternal influence encouraged young Southern's early tinkering in a home workshop, sparking his curiosity about mechanics and technology amid the challenges of an industrial environment where children often navigated mill-adjacent streets and countryside explorations freely. As the first in his family to pursue university studies, Southern attended Burnley Grammar School during his childhood, where the selective grammar system offered a pathway out of manual labor, though it demanded exceptional determination in a post-war setting of resource scarcity and social mobility barriers.[13] From an early age, Southern displayed an inventive bent, constructing miniature looms from cotton bobbins, string, and darning needles to decipher the weaving patterns observed in Burnley's mills—a hands-on pursuit that highlighted his innate interest in technology and foreshadowed his later scientific career. He later reflected on this period as foundational to his problem-solving mindset, noting, “I think my approach to science is as a problem solver, I've always been like that... Even as a child, I liked dreaming up solutions, and I've always been fascinated by technology.” These experiences in 1940s Lancashire, blending industrial grit with personal ingenuity, profoundly influenced his trajectory toward academia.[7]

Education

Southern earned a Bachelor of Science degree with honors in Chemistry from the University of Manchester in 1958, where he received foundational training in chemical principles and laboratory techniques essential for his subsequent biochemical pursuits.[14] He continued his studies at the University of Glasgow, completing a PhD in chemistry in 1962 under the supervision of Dr. W.R. Rees. His doctoral thesis, titled Studies on synthetic and naturally occurring enzyme metabolites, explored the chemical properties and reactions of metabolites associated with enzymatic processes, providing him with advanced expertise in biochemical analysis.[5][15] During his PhD research, Southern transitioned toward investigations of nucleic acids, gaining early exposure to the structural and functional aspects of DNA and RNA that would inform his groundbreaking later work in molecular biology.[14]

Professional career

Academic positions

Southern began his independent academic career at the University of Edinburgh, joining the Medical Research Council (MRC) Mammalian Genome Unit in the Department of Zoology in 1967, where he focused on DNA structure and sequencing methods.[6] In 1985, he relocated to the University of Oxford, assuming the Whitley Chair of Biochemistry and becoming a Fellow of Trinity College.[16][17] He progressed through departmental leadership, serving as Head of the Department of Biochemistry until 1991.[18] Southern held the professorship until his retirement in 2005, after which he was appointed Emeritus Professor of Biochemistry at Oxford, maintaining his affiliation as an Honorary Fellow of Trinity College.[19][9]

Commercial ventures and philanthropy

In 1995, Edwin Southern founded Oxford Gene Technology (OGT), a biotechnology company aimed at commercializing his invention of DNA microarray technology for genetic analysis.[9] He served as the company's leader, guiding its development into a provider of genetic research tools until its acquisition by Sysmex Corporation in 2017, which made OGT a wholly owned subsidiary.[9] A key early milestone for OGT was its successful defense of Southern's microarray patents in a 1999 lawsuit against Affymetrix, a U.S. gene-chip maker; the case, initiated over infringement claims on patents filed as early as 1988, was settled in OGT's favor in 2004 after court rulings affirmed the validity and exclusivity of Southern's intellectual property.[7] Royalties from the licensing of microarray technology through OGT enabled Southern to establish philanthropic initiatives focused on scientific advancement. In 2000, he founded the Kirkhouse Trust, a UK-registered charity dedicated to supporting independent research in plant sciences, particularly the breeding of grain legumes for improved food security in developing regions such as Africa and India.[20] Southern has maintained an active role as the trust's founder and trustee, overseeing grants that apply genomic methods to crop improvement.[20] Similarly, in 2002, he created the Edina Trust to advance science education, with an emphasis on enhancing primary school programs in the UK through hands-on initiatives that foster interest in scientific inquiry.[21] Following the 2017 sale of OGT, Southern directed the proceeds toward expanding the Kirkhouse Trust's scope, increasing grants for genomics and agriculture research to address challenges like crop resilience in semi-arid areas.[9] He has not pursued major new commercial ventures since the OGT transaction.[17]

Research contributions

Southern blot

The Southern blot technique, developed by Edwin Southern in 1973 while at the Medical Research Council (MRC) Mammalian Genome Unit in Edinburgh and first published in 1975, addressed the challenge of identifying specific DNA sequences within complex mixtures of fragments separated by gel electrophoresis.[22] Southern, working in his laboratory on mouse DNA to locate particular genes, realized that the permeability of agarose gels allowed DNA to be eluted and captured on a membrane, enabling subsequent probing without extracting bands from the gel itself. This innovation built upon prior advances in agarose gel electrophoresis for nucleic acids, introduced in the early 1960s, by adding a transfer and detection step that made sequence-specific analysis feasible at the time.[22] The procedure begins with the digestion of genomic DNA using restriction endonucleases to generate fragments of varying lengths.[22] These fragments are then separated by size via agarose gel electrophoresis under conditions that resolve them based on molecular weight.[22] The gel is treated with alkali to denature the double-stranded DNA into single strands, facilitating subsequent hybridization.[22] The denatured DNA is transferred from the gel to a nitrocellulose membrane through capillary action, where it binds irreversibly in a position that mirrors its electrophoretic pattern—a process Southern optimized using a stack of absorbent materials to drive the flow.[22] The membrane is then incubated with a radiolabeled single-stranded DNA probe complementary to the target sequence, allowing hybridization under stringent conditions to ensure specificity.[22] Finally, unbound probe is washed away, and the hybridized probe is detected via autoradiography, revealing bands corresponding to the target DNA fragments.[22] The method's name derives directly from its inventor, Edwin Southern, in a playful convention that later inspired analogous techniques like Northern blotting for RNA; Southern later described this naming as a lighthearted choice rather than a formal one. Following publication in the Journal of Molecular Biology, the technique was soon applied to restriction fragment length polymorphism analysis and gene mapping, providing evidence for multigene families, including the human β-globin gene cluster.[22] Over time, the Southern blot evolved to incorporate non-radioactive detection methods, such as chemiluminescent or fluorescent labels using enzymes like horseradish peroxidase conjugated to probes, reducing hazards and improving safety in routine lab use since the 1980s.[23] It also became a standard for quantitative assessment of gene copy number, where band intensity, normalized against standards, indicates amplification or deletion events in genomic DNA, aiding studies in oncology and genetic disorders.

DNA microarray

In the late 1980s, while serving as Professor of Biochemistry at the University of Oxford, Edwin Southern conceived the idea of DNA microarrays to enable parallel analysis of multiple DNA sequences, inspired by the limitations of sequential sequencing methods and discussions on oligonucleotide hybridization during a 1987 meeting in Japan.[24] This built briefly on his earlier Southern blot technique as a precursor for detecting specific DNA sequences through hybridization.[25] Southern's initial experiments, conducted with PhD student Uwe Maskos starting in 1987, involved spotting presynthesized oligonucleotides onto nylon membranes or synthesizing them in situ on glass supports using controlled pore glass to facilitate high-density arrays.[26] These early arrays, demonstrated in a 1992 study, allowed for the hybridization of target DNA to immobilized probes, marking the first practical implementation of multiplexed DNA analysis on solid supports.[27] Key advancements in the 1990s included Southern's patents on array fabrication and hybridization methods, such as UK Patent GB 2247880 (filed 1989, granted 1992) and related international filings, which covered the immobilization of oligonucleotides for sequence detection via fluorescence labeling.[24] Technically, the arrays employed either spotting of pre-made DNA probes (up to 19-mers initially) or in situ synthesis via phosphoramidite chemistry on glass slides, followed by hybridization with fluorescently tagged target DNA and scanning for signal intensity to quantify binding.[28] These innovations enabled high-throughput screening, with arrays accommodating thousands of probes in a compact format, far surpassing the single-sequence limitations of earlier techniques.[26] Southern commercialized the technology through Oxford Gene Technology (OGT), founded in 1995, which licensed the patents for applications in gene expression profiling—measuring mRNA levels across genomes—and DNA sequencing by hybridization.[9] OGT's arrays were sublicensed to companies like Agilent Technologies, facilitating widespread adoption in genomics for mapping gene functions and identifying disease-related variants.[24] In diagnostics and pharmacogenomics, the technology supported personalized medicine by detecting genetic polymorphisms influencing drug responses, such as in cancer therapies.[29] The impact of Southern's DNA microarray revolutionized high-throughput biological research, playing a pivotal role in the Human Genome Project era by accelerating gene discovery and expression analysis across species.[26] However, challenges included scaling production for uniform probe density and resolving patent disputes, notably a 2000 UK court victory for OGT against Affymetrix, which affirmed Southern's core claims on array hybridization and generated licensing revenues exceeding £100 million to fund philanthropic trusts.[30] These legal wins, stemming from suits filed in 1999, ensured the technology's broad accessibility while overcoming early manufacturing hurdles like probe alignment precision.[24]

Awards and honors

Major scientific awards

Edwin Southern received the Canada Gairdner International Award in 1990 for his discovery, development, and application of gel electrophoresis methods that enable the separation and identification of specific proteins and nucleic acids, fundamentally advancing DNA analysis techniques.[11] In 1998, he was awarded the Royal Medal by the Royal Society, recognizing his development of the Southern blot method—a key innovation for transferring DNA fragments from electrophoretic gels to membranes for hybridization analysis—and his further contributions to studying specific DNA sequences and chromosome structures using oligonucleotide hybridization.[1] Southern shared the Albert Lasker Award for Clinical Medical Research in 2005 with Alec Jeffreys, honoring their revolutionary advancements in genetic diagnostics and forensics through Southern blotting, which detects specific DNA sequences in complex genomes, and DNA fingerprinting, which has transformed gene mapping, disease diagnosis, and identification processes.[8]

Knighthood and other distinctions

In 2003, Southern was appointed Knight Bachelor in the Birthday Honours for services to the development of DNA fingerprinting.[31] Southern was elected a Fellow of the Royal Society (FRS) in 1983 in recognition of his contributions to molecular biology.[1] He is also an Honorary Fellow of the Royal Society of Edinburgh (HonFRSE), elected in 2012.[1][32] He was elected a Foreign Honorary Member of the American Academy of Arts and Sciences in 1988.[33] Southern has received several honorary degrees, including a Doctor of Science (DSc) from the University of Glasgow in 2004 for his notable contributions to science, and an honorary degree in Medicine and Surgery from the University of Padua in 1988.[34][35] Following his retirement, he was appointed Emeritus Professor of Biochemistry at the University of Oxford and Honorary Fellow of Trinity College, Oxford.[17] Southern's invention of the Southern blot has had a lasting legacy in scientific nomenclature, inspiring the terms "Northern blot" for RNA detection and "Western blot" for protein analysis, reflecting the technique's foundational influence on molecular biology methods.[36]

References

  1. Sir Edwin Southern FMedSci FRS - Fellow Detail Page | Royal Society
  2. Edwin Southern: Southern Blot Inventor - Molecular Biology - Scribd
  3. Bicentenary Way - The University of Manchester
  4. Edwin Southern - International Livestock Research Institute
  5. Problem Solved: An Interview with Sir Edwin Southern - PMC - NIH
  6. https://www.thelancet.com/article/S0140-6736(05
  7. Southern blotting and DNA fingerprinting - Lasker Foundation
  8. OGT company founder Prof. Sir Edwin Southern
  9. Edwin M. Southern - Gairdner Foundation Award Winner
  10. DNA pioneer Professor Sir Edwin Southern on the future of genomics
  11. Edwin Southern, DNA blotting, and microarray technology: A case ...
  12. Studies on synthetic and naturally occurring enzyme metabolites
  13. https://theses.gla.ac.uk/79496/1/13849481.pdf
  14. [PDF] Top 100 living contributors to biotechnology - The Golden Rice Project
  15. Ed Southern | Trinity College Oxford
  16. Sir George Radda CBE FMedSci FRS - Department of Biochemistry
  17. UOA05-15: Oxford Gene Technology: the detection of genetic ...
  18. Board of Trustees | Kirkhouse Trust
  19. Inspiring young minds: Life's partnership with the Edina Trust
  20. Southern blotting - PubMed
  21. Problem Solved: An Interview with Sir Edwin Southern
  22. Edwin Southern, DNA blotting, and microarray technology: A case ...
  23. The emergence and diffusion of DNA microarray technology - PMC
  24. Studies of oligonucleotide interactions by hybridisation to arrays - NIH
  25. The next generation of microarray research: applications in ... - Nature
  26. The DNA Microarray | The Scientist
  27. Affymetrix loses first round of patent battle - Nature
  28. Cambridge professors knighted in birthday honours | Higher education
  29. Professor Sir Edwin Southern - Royal Society of Edinburgh
  30. University news - Archive of news - 2004 ... - University of Glasgow
  31. Honorary degrees | Università di Padova
  32. Southern, northern, western (and eastern?) - Bitesize Bio
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