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Robert Williamson (geneticist)

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Robert Williamson
AC FAA FRA
Born1938 (age 85–86)
Cleveland, Ohio, USA
Alma materUniversity College London
AwardsOfficer of the Order of Australia (2004)
Scientific career
FieldsHuman Genetics; Molecular genetics
InstitutionsMurdoch Children's Research Institute, University of Melbourne
Websitewww.rch.org.au/alumni/alumni_profiles/Williamson,_Bob_________AO/

Robert Williamson AO FAA (born 1938) is a retired British-Australian molecular biologist who specialised in the mapping, gene identification, and diagnosis of human genetic disorders.

Career

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Williamson was born in Cleveland, Ohio, to Scottish parents. He was educated at the Bronx High School of Science in New York and then Wandsworth School in South London after his parents returned to the UK, before studying at University College London.[1] From 1963 he was lecturer, then senior lecturer, in developmental biology at the University of Glasgow. From 1976 he was Professor and head of Molecular Genetics and Biochemistry at St Mary's Hospital Medical School, University of London.[2]

He emigrated to Melbourne, Australia in 1995 to be Director of the Murdoch Children's Research Institute (then the Murdoch Institute) and Professor of Medical Genetics at the University of Melbourne. He edited several books on genetic engineering and on the ethics of the new genetic sciences.

Since his retirement in 2004, Williamson has been the Secretary for Science Policy at the Australian Academy of Science and an Honorary Senior Principal Fellow (Professor) at the University of Melbourne.

Research

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Williamson began his career working on haemoglobin synthesis in reticulocytes (immature red blood cells) and thalassaemias (inherited blood disorders). As a lecturer at the University of Glasgow, he studied human gene organisation and expression. In 1970, he was the solo author of a paper that provided the dual discovery of the origin of cell-free DNA and the nucleosome organisation of DNA in chromosomes, including the first description of the "nucleosome ladder".[3] Decades later, the geneticists Steven Henikoff and George Church hailed Williamson's report as “a remarkably prescient paper,” adding: “The simultaneous discovery of the nucleosome ladder and the origin of [cell-free] cfDNA in 1970 was thus correctly interpreted by Williamson, respectively 3 years and nearly 3 decades before the biological significance of nucleosomes and the clinical utility of cfDNA were appreciated.”[4]

Williamson chose not to follow up on those results, turning his attention to messenger RNA and then the study of globin genes and the thalassaemias. In 1974, Williamson's group demonstrated that severe alpha-thalassaemia is due to a deletion in the alpha globin gene,[5] and subsequently that delta-beta thalassaemia was attributed to a deletion in the beta globin gene.[6] From his new position at St. Mary's Hospital Medical School, Williamson's group went on to clone the human alpha-, beta- and gamma-globin genes from cDNAs, and used them to deduce their genomic structures.

By 1980, Williamson and colleagues began applying the discovery of DNA markers called restriction fragment length polymorphisms to perform linkage mapping to locate the position of important human disease genes. In 1982, working with Kay Davies, Williamson's group narrowed down the location of the X-linked Duchenne muscular dystrophy gene.[7] Williamson is best known for his research on the genetics of cystic fibrosis. In 1985, Williamson lead one of three teams that independently mapped the gene mutated in cystic fibrosis to chromosome 7,[8] sparking an intense international race to identify the gene. His group came close to isolating the defective gene, reporting a strong candidate in 1987,[9] only to be scooped by Lap-Chee Tsui, Francis Collins and colleagues in 1989.[10]

Throughout the 1980s, Williamson and colleagues pursued the use of random DNA markers to map mutated genes responsible for several other major genetic disorders, including myotonic dystrophy, Friedreich's ataxias, coronary artery disease, craniofacial abnormalities, and Alzheimer's disease. In 1988, Williamson's group also developed the first method for genetic testing using cheek buccal epithelial cells obtained by a simple mouthwash.[11] In 1991, John Hardy, a lecturer in Williamson's department, identified the first mutation associated with Alzheimer's disease in the gene encoding the amyloid precursor protein (APP).[12]

Williamson was an early proponent of human gene therapy, writing presciently in 1982: "Gene therapy is not yet possible, but may become feasible soon, particularly for well understood gene defects. Although treatment of a patient raises no ethical problems once it can be done well, changing the genes of an early embryo is more difficult, controversial and unlikely to be required clinically."[13] Following the discovery of the CF gene in 1989, he turned his attention to developing strategies for gene therapy for CF patients in his final years at St. Mary's, including a non-viral proof-of-concept study in the inaugural issue of Nature Medicine.[14]

Williamson recruited and mentored many leading molecular geneticists during his two decades at St. Mary's Hospital, including Royal Society Fellows Dame Kay Davies, Stephen D. M. Brown, Gillian Bates and John Hardy. Davies recalled: “With Bob, nothing was impossible; he always knew someone in the field who would be able to help whenever we needed a new technique or vector for cloning. He taught me how much more successful you could be as a scientist if you were collaborative and had an extensive network of basic and clinical scientists.”[15] Hardy acknowledged that the “first 13 grant applications I wrote were unsuccessful and without the continuing support of Bob, our efforts would have foundered.”[16]

In 1995, Williamson moved from London to Melbourne, Australia, to become Director of the Murdoch Children's Research Institute, taking over from David Danks,[17] a clinical geneticist who had trained with Victor A. McKusick. Williamson directed a broad research portfolio on a range of molecular genetics technologies, such as preimplantation genetic diagnosis[18] used in conjunction with in vitro fertilisation and Friedreich's ataxia[19] He established training for genetic counsellors and public health paediatricians[20] and continued working at the interface of ethics genetics, with a particular interest in Aboriginal genomics.[21] Williamson successfully broadened the orientation of the Murdoch Institute, growing it to some 600 staff by the time he retired in 2005, pursuing research on ethics, public health, and genetics of complex diseases.

Williamson has published more than 400 scientific papers.[22] He is an eloquent commentator and prominent evangelist for the societal benefits of genetic testing, from proposing community-wide carrier screening for cystic fibrosis[23] to universal DNA testing.[24]

Honours and awards

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In 1994, he was awarded the King Faisal International Prize in Medicine, together with W. French Anderson, for medical applications of molecular genetics.[25]

In 1997, he received an Honorary MD degree from the University of Turku, Finland.

He was elected to the Royal Society in 1999.[22] He is also a Fellow of the Royal College of Physicians, the Royal College of Pathologists and the Australian Academy of Science (2001).

In 2004, he was appointed an Officer of the Order of Australia (AO).

References

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  1. ^ Who's Who 2019. A & C Black, London. 2018. ISBN 978-1-472-94758-1.
  2. ^ "Professor Bob Williamson". Murdoch Children's Research Institute. Retrieved 15 August 2018.
  3. ^ Williamson, R. Properties of rapidly labelled deoxyribonucleic acid fragments isolated from the cytoplasm of primary cultures of embryonic mouse liver cells. J. Mol. Biol. 51, 157-160 (1970). https://doi.org/10.1016/0022-2836(70)90277-9
  4. ^ Henikoff, S. & Church, G.M. Simultaneous Discovery of Cell-Free DNA and the Nucleosome Ladder. Genetics 209, 27-29 (2018). https://doi.org/10.1534/genetics.118.300775
  5. ^ Ottolenghi, S. et al. Gene deletion as the cause of α thalassaemia: The severe form of α thalassaemia is caused by a haemoglobin gene deletion. Nature 251, 389-392 (1974). https://doi.org/10.1038/251389a0
  6. ^ Ottolenghi, S. et al. δβ-Thalassemia is due to a gene deletion. Cell 9, 71-80 (1976). https://doi.org/10.1038/251389a0
  7. ^ Murray, J.M. et al. Linkage relationship of a cloned DNA sequence on the short arm of the X chromosome to Duchenne muscular dystrophy. Nature 300, 69-71 (1982). https://doi.org/10.1038/300069a0
  8. ^ Wainwright, B.J. et al. Localization of cystic fibrosis locus to human chromosome 7cen–q22. Nature 318, 384-385 (1985). https://doi.org/10.1038/318384a0
  9. ^ Estivill, X. et al. A candidate for the cystic fibrosis locus isolated by selection for methylation-free islands. Nature 326, 840-846 (1987). https://doi.org/10.1038/326840a0
  10. ^ Kevin Davies. The search for the cystic fibrosis gene. New Scientist 20 October 1989. https://www.newscientist.com/article/mg12416873-900/
  11. ^ Lench, N. et al. Simple non-invasive method to obtain DNA for gene analysis. Lancet 331, 1356-1368 (1988). https://doi.org/10.1016/S0140-6736(88)92178-2
  12. ^ Goate, A. et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 349, 704-706 (1991). https://doi.org/10.1038/349704a0
  13. ^ Williamson, B. Nature 298, 416-418 (1982). https://doi.org/10.1038/298416a0
  14. ^ Caplen, N.J. et al. Nature Medicine 1, 39-46 (1995).
  15. ^ Davies, K.E. The Long Journey from Diagnosis to Therapy. Ann. Rev. Genomics & Human Genet. 21, 1-13 (2020). https://doi.org/10.1146/annurev-genom-112019-083518
  16. ^ Hardy, J. The discovery of Alzheimer-causing mutations in the APP gene and the formulation of the “amyloid cascade hypothesis”. FEBS Journal 284, 1040-1044 (2017). https://doi.org/10.1111/febs.14004
  17. ^ Choo, K.H.A. "David M. Danks, M.D., A.O. (June 4, 1931–July 8, 2003): Founder, Murdoch Childrens Research Institute". American Journal of Human Genetics 73: 981–985 (2003). doi:10.1086/379383.
  18. ^ Wilton, L., Williamson, R., McBain J., Edgar, D., and Voullaire, L. “Birth of a Healthy Infant after Preimplantation Confirmation of Euploidy by Comparative Genomic Hybridisation” N. Engl. J. Med, 345:1537-1541 (2001).
  19. ^ Delatycki, M.B., Williamson, R. and Forrest, S.M. “Friedreich Ataxia; an overview.” J. Med. Genet. 37:1-8 (2000).
  20. ^ Collins, V., Halliday, J., Kahler, S., and Williamson, R. “Parents’ Experience with Genetic Counseling After the Birth of a Baby with a Genetic Disorder: An Exploratory Study.” J. Genet. Coun. 10:53-72 (2001).
  21. ^ Dodson, M. and Williamson, R. “Indigenous People and the Morality of the Human Genome Diversity Project.” J. Med. Ethics 25:204-208 (1999).
  22. ^ a b "Robert Williamson". Royal Society. 12 August 2015. Retrieved 12 August 2018.
  23. ^ Williamson, R. Universal community carrier screening for cystic fibrosis? Nature Genetics 3, 195-201 (1993). https://doi.org/10.1038/ng0393-195
  24. ^ Williamson, R. & Duncan, R. DNA testing for all. Nature 418, 585-586 (2002). https://doi.org/10.1038/418585a
  25. ^ "Professor Robert Williamson". King Faisal Prize. 10 October 2012. Retrieved 12 August 2018.
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